J Santos-Alvarez

Hospital Universitario Virgen Macarena, Hispalis, Andalusia, Spain

Are you J Santos-Alvarez?

Claim your profile

Publications (22)74.09 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pancreastatin is one of the regulatory peptides derived from intracellular and/or extracellular processing of chromogranin A, the soluble acidic protein present in the secretory granules of the neuroendocrine system. While the intracellular functions of chromogranin A include formation and maturation of the secretory granule, the major extracellular functions are generation of biologically active peptides with demonstrated autocrine, paracrine or endocrine activities. In this review, we will focus on the metabolic function of one of these peptides, pancreastatin, and the mechanisms underlying its effects. Many different reported effects have implicated PST in the modulation of energy metabolism, with a general counterregulatory effect to that of insulin. Pancreastatin induces glycogenolysis in liver and lipolysis in adipocytes. Metabolic effects have been confirmed in humans. Moreover, naturally occurring human variants have been found, one of which (Gly297Ser) occurs in the functionally important carboxy-terminus of the peptide, and substantially increases the peptide's potency to inhibit cellular glucose uptake. Thus, qualitative hereditary alterations in pancreastatin's primary structure may give rise to interindividual differences in glucose and lipid metabolism. Pancreastatin activates a receptor signaling system that belongs to the seven-spanning transmembrane receptor coupled to a Gq-PLCβ-calcium-PKC signaling pathway. Increased pancreastatin plasma levels, correlating with catecholamines levels, have been found in insulin resistance states, such as gestational diabetes or essential hypertension. Pancreastatin plays important physiological role in potentiating the metabolic effects of catecholamines, and may also play a pathophysiological role in insulin resistance states with increased sympathetic activity.
    Regulatory Peptides 10/2010; 165(1):71-7. DOI:10.1016/j.regpep.2010.10.004 · 2.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adipose tissue is an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that may be present in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response, innate and adaptive response, both in normal and pathological conditions. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response.
    Mediators of Inflammation 03/2010; 2010:568343. DOI:10.1155/2010/568343 · 3.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Adipose tissue is no longer considered mere energy storage, but an important endocrine organ that produces many signals in a tightly regulated manner. Leptin is one of the most important hormones secreted by the adipocyte, with a variety of physiological roles related with the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response both in normal as well as in pathological conditions. Leptin's modulation of the immune system is exerted at the development, proliferation, anti-apoptotic, maturation, and activation levels. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. Both the innate and adaptative immune responses are regulated by leptin. Every cell type involved in immunity can be modulated by leptin. In fact, leptin receptors have been found in neutrophils, monocytes, and lymphocytes, as well as belonging to the family of class I cytokine receptors. Moreover, leptin activates similar signaling pathways to those engaged by other members of the family. The overall leptin action in the immune system is a proinflammatory effect, activating proinflammatory cells, promoting T-helper 1 responses, and mediating the production of the other proinflammatory cytokines, such as tumor necrosis factor- α, interleukin (IL)-2, or IL-6. Leptin receptor is also upregulated by proinflammatory signals. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response, and could have also a permissive role in the development of autoimmune diseases.
    Current Immunology Reviews 10/2008; 4(4):230-234. DOI:10.2174/157339508786447841
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adipose tissue is no longer considered as a mere energy store, but an important endocrine organ that produces many signals in a tightly regulated manner. Leptin is one of the most important hormones secreted by the adipocyte, with a variety of physiological roles related with the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. Leptin’s modulation of the immune system is exerted at the development, proliferation, anti-apoptotic, maturation, and activation levels. The role of leptin in regulating the immune response has been assessed in vitro as well as in clinical studies. Both the innate and adaptive immune responses are regulated by leptin. Every cell type involved in immunity can be modulated by leptin. In fact, leptin receptors have been found in neutrophils, monocytes, and lymphocytes, and the leptin receptor belongs to the family of class I cytokine receptors. Moreover, leptin activates similar signaling pathways to those engaged by other members of the family. The overall leptin action in the immune system is a proinflammatory effect, activating proinflammatory cells, promoting T-helper 1 responses, and mediating the production of other proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-2, or IL-6. Leptin receptor is also upregulated by proinflammatory signals. Thus, leptin is a mediator of the inflammatory response, and could have also a permissive role in the development of autoimmune diseases.
    12/2006: pages 79-90;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Leptin is a an adipocyte-secreted hormone that regulates weight centrally. However, the leptin receptor is expressed not only in the central nervous system, but also in peripheral tissues, such as haematopoietic and immune systems. Therefore, the physiological role of leptin should not be limited to the regulation of food intake and energy expenditure. Moreover, the leptin receptor bears homology to members of the class I cytokine family, and recent data have demonstrated that leptin is able to modulate the immune response. Thus, the leptin receptor is expressed in human peripheral blood mononuclear cells, mediating the leptin effect on proliferation and activation. In vitro activation and HIV infection in vivo induce the expression of the long isoform of the leptin receptor in mononuclear cells. Also, leptin stimulates the production of proinflammatory cytokines from cultured monocytes and enhances the production of Th1 type cytokines from stimulated lymphocytes. Moreover, leptin has a trophic effect on monocytes, preventing apoptosis induced by serum deprivation. Leptin stimulation activates JAK-STAT, IRS-1-PI3K and MAPK signalling pathways. Leptin also stimulates Tyr-phosphorylation of the RNA-binding protein Sam68 mediating the dissociation from RNA. In this way, leptin signalling could modulate RNA metabolism. These signal transduction pathways provide possible mechanisms whereby leptin may modulate activation of peripheral blood mononuclear cells. Therefore, these data support the hypothesis regarding leptin as a proinflammatory cytokine with a possible role as a link between the nutritional status and the immune response. Moreover, these immunoregulatory functions of leptin could have some relevance in the pathophysiology of obesity.
    Clinical & Experimental Immunology 08/2003; 133(1):11-9. DOI:10.1046/j.1365-2249.2003.02190.x · 3.28 Impact Factor
  • Víctor Sánchez-Margalet · José Santos-Alvarez · Sandra Díaz-Troya
    Methods in Molecular Biology 02/2003; 228:187-94. DOI:10.1385/1-59259-400-X:187 · 1.29 Impact Factor
  • 12/2001: pages 247-262;
  • C González-Yanes · J Santos-Alvarez · V Sánchez-Margalet
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreastatin (PST) is one of the chromogranin A (CGA)-derived peptides with known biological activity. It has a general inhibitory effect on secretion in many exocrine and endocrine systems including the heart atrium. Besides, a role of PST as a counter-regulatory peptide of insulin action has been proposed in the light of its effects on glucose and lipid metabolism in the liver and adipose tissue, where receptors and signaling have been described. Galpha(q/11) pathway seems to mediate PST action. Since PST has been shown to function as a typical calcium-dependent hormone, and increased plasma levels have been found in essential hypertension correlating with catecholamines, we sought to study its possible interaction and signaling in heart membranes. Here, we are characterizing specific PST binding sites and signaling in rat heart membranes. We have found that PST receptor has a K(d) of 0.5 nM and a B(max) of 34 fmol/mg of protein. The PST binding is inhibited by guanine nucleotides, suggesting the functional coupling of the receptor with GTP binding proteins (G proteins). Moreover, PST dose-dependently increases GTP binding to rat heart membranes. Finally, we have studied PST signaling-effector system by measuring phospholipase C (PLC) activity using blocking antibodies against different G proteins and PLC isoforms. We have found that PST stimulates PLCbeta(2)>PLCbeta(1)>PLCbeta(3) by activating Galpha(16) in rat heart membranes. These data suggest that PST may modulate the cardiac function.
    Cellular Signalling 01/2001; 13(1):43-9. DOI:10.1016/S0898-6568(00)00127-3 · 4.47 Impact Factor
  • José Santos-Alvarez · Víctor Sánchez-Margalet
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreastatin, a chromogranin A derived peptide, exerts a glycogenolytic effect on the hepatocyte. This effect is initiated by binding to membrane receptors which are coupled to pertussis toxin insensitive G proteins belonging to the Gq/11 family. We have recently solubilized active pancreastatin receptors from rat liver membranes still functionally coupled to G proteins. Here, we have purified pancreastatin receptors by a two-step procedure. First, pancreastatin receptors with their associated Gq/11 regulatory proteins were purified from liver membranes by lectin absorption chromatography on wheat germ agglutinin immobilized on agarose. A biotinylated rat pancreastatin analog was tested for binding to liver membranes before using it for affinity purification. Unlabeled biotinylated rat pancreastatin competed for 125I-labeled [Tyr0]PST binding to solubilized receptors with a Kd = 0.27 nM, comparable to that of native pancreastatin. The biotinylated analog was immobilized on streptavidin-coated Sepharose beads and used to further affinity purify wheat germ agglutinin eluted receptor material. Specific elution at low pH showed that the receptor protein was purified as an 80-kDa protein in association with a G protein of the q/11 family, as demonstrated by specific immunoblot analysis. The specificity of the receptor band was assessed by chemical cross-linking of the purified material followed by SDS-PAGE and autoradiography. In conclusion, we have purified pancreastatin receptor as a glycoprotein of 80 kDa physically associated with a Gq/11 protein.
    Archives of Biochemistry and Biophysics 07/2000; 378(1):151-6. DOI:10.1006/abbi.2000.1789 · 3.04 Impact Factor
  • V Sánchez-Margalet · C González-Yanes · J Santos-Alvarez · S Najib
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreastatin, a chromogranin A-derived peptide widely distributed throughout the neuroendocrine system, has a general inhibitory effect on endocrine secretion and a counterregulatory effect on insulin action. We have recently described the cross-talk of pancreastatin with insulin signaling in rat hepatoma cells (HTC), where it inhibits insulin action and signaling through the serine phosphorylation of the insulin receptor, thereby impairing tyrosine kinase activity. Here, we have characterized pancreastatin receptors and signaling in HTC cells. The pancreastatin effector systems were studied by determining phospholipase C activity in HTC membranes and mitogen-activated protein kinase (MAPK) phosphorylation activity in HTC cells. Binding studies with radiolabeled pancreastatin showed a population of high affinity binding sites, with a B(max) of 8 fmol/mg protein and a K(d) of 0.6 nM. Moreover, we assessed the coupling of the receptor with a G protein system by inhibiting the binding with guanine nucleotide and by measuring the GTP binding to HTC membranes. We found that pancreastatin receptor was coupled with a G alpha(q/11) protein which activates phospholipase C-beta(1) and phospholipase C-beta(3), in addition to MAPK via both beta gamma and alpha(q/11).
    European Journal of Pharmacology 07/2000; 397(2-3):229-35. DOI:10.1016/S0014-2999(00)00253-3 · 2.68 Impact Factor
  • Journal of Chromatography A 06/2000; 882(1). · 4.26 Impact Factor
  • V Sánchez-Margalet · C González-Yanes · J Santos-Alvarez · S Najib
    Advances in Experimental Medicine and Biology 02/2000; 482:247-62. · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Leptin is an adipocyte-secreted hormone that centrally regulates weight control. However, leptin receptor is expressed not only in the central nervous system, but also in other systems such as reproductive and hematopoietic tissues. Human leptin has previously been shown to enhance cytokine production by murine peritoneal macrophages and human circulating monocytes. In this paper we have assessed the presence of leptin receptors in peripheral human T lymphocytes and we have studied their functional role. Both CD4(+) and CD8(+) T lymphocytes express leptin receptors. Moreover, we show that human leptin dose-dependently enhances proliferation and activation of human circulating T lymphocytes when they are costimulated by PHA or Con A. Leptin alone was not able to activate T lymphocytes. To confirm a direct effect of leptin on T lymphocytes, monocytes were extracted by adhesion to culture flasks. The early activation surface marker CD69 was then induced in both CD4(+) and CD8(+) T lymphocytes after 8 h stimulation with PHA or Con A. Leptin dose-dependently enhanced stimulated CD69 expression. Moreover, leptin dose-dependently enhanced the expression of the late activation markers CD25 and CD71 in both CD4(+) and CD8(+) T lymphocytes after 48 h stimulation with PHA or Con A. Finally, we have found that leptin modulates CD4(+) T lymphocyte activation toward Th1 phenotype by stimulating the synthesis of IL-2 and IFN-gamma. These results demonstrate the presence of the leptin receptor in human circulating CD4(+) and CD8(+) T lymphocytes and a functional role of leptin as a modulator (enhancer) of lymphocyte stimulation with a shift toward Th1 cytokine-production profile. This function of leptin may have some relevance in the pathophysiology of immunologic alterations related to obesity.
    Cellular Immunology 02/2000; 199(1):15-24. DOI:10.1006/cimm.1999.1594 · 1.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreastatin (PST), a chromogranin A derived peptide with an array of effects in different tissues, has a role as a counterregulatory hormone of insulin action in hepatocytes and adipocytes, regulating glucose, lipid and protein metabolism. We have previously characterized PST receptors and signaling in rat hepatocytes, in which PST functions as a calcium-mobilizing hormone. In the present work we have studied PST receptors as well as the signal transduction pathways generated upon PST binding in adipocyte membranes. First, we have characterized PST receptors using radiolabeled PST as a ligand. Analysis of binding data indicated the existence of one class of binding sites, with a B(max) of 5 fmol/mg of protein and a K(d) of 1 nM. In addition, we have studied the G protein system that couples the PST receptor by gamma-(35)S-GTP binding studies. We have found that two G protein systems are involved, pertussis toxin-sensitive and -insensitive respectively. Specific anti-G protein alpha subtype sera were used to block the effect of pancreastatin receptor activation. Galpha(q/11) and to a lesser extent Galpha(i1,2) are activated by PST in rat adipocyte membranes. On the other hand, adenylate cyclase activity was not affected by PST. Finally, we have studied the specific phospholipase C isoform that is activated in response to PST. We have found that PST receptor is coupled to PLC-beta(3) via Galpha(q/11) activation in adipocyte membranes.
    Biochimica et Biophysica Acta 09/1999; 1451(1):153-62. DOI:10.1016/S0167-4889(99)00084-1 · 4.66 Impact Factor
  • J Santos-Alvarez · V Sánchez-Margalet
    [Show abstract] [Hide abstract]
    ABSTRACT: In the liver, pancreastatin exerts a glycogenolytic effect through interaction with specific receptors, followed by activation of phospholipase C and guanylate cyclase. Pancreastatin receptor seems to be coupled to two different G protein systems: a pertussis toxin-insensitive G protein that mediates activation of phospholipase C, and a pertussis toxin sensitive G protein that mediates the cyclic GMP production. The aim of this study was to identify the specific G protein subtypes coupling pancreastatin receptors in rat liver membranes. GTP binding was determined by using gamma-35S-GTP; specific anti-G protein alpha subtype sera were used to block the effect of pancreastatin receptor activation. Activation of G proteins was demonstrated by the incorporation of the photoreactive GTP analogue 8-azido-alpha-32P-GTP into liver membranes and into specific immunoprecipitates of different Galpha subunits from soluble rat liver membranes. Pancreastatin stimulation of rat liver membranes increases the binding of gamma-35S-GTP in a time- and dose-dependent manner. Activation of the soluble receptors still led to the pancreastatin dose-dependent stimulation of gamma-35S-GTP binding. Besides, WGA semipurified receptors also stimulates GTP binding. The binding was inhibited by treatment with anti-Galphaq/11 (85%) and anti-Galphai1,2 (15%) sera, whereas anti-Galphao,i3 serum failed to affect the binding. Finally, pancreastatin stimulates GTP photolabeling of particulate membranes. Moreover, it specifically increased the incorporation of 8-azido-alpha-32P-GTP into Galphaq/11 and Galpha, but not into Galphao,i3 from soluble rat liver membranes. In conclusion, pancreastatin stimulation of rat liver membranes led to the activation of Galphaq/11 and Galphai1,2 proteins. These results suggest that Galphaq/11 and Galphai1,2 may play a functional role in the signaling of pancreastatin receptor by mediating the production of IP3 and cGMP respectively.
    Journal of Cellular Biochemistry 07/1999; 73(4):469-77. · 3.37 Impact Factor
  • José Santos-Alvarez · Raimundo Goberna · Victor Sánchez-Margalet
    [Show abstract] [Hide abstract]
    ABSTRACT: The Ob gene product, leptin, is an adipocyte-secreted hormone that centrally regulates weight control. However, leptin receptor is expressed not only in the central nervous system, but also in other systems such as reproductive and hematopoietic tissues. Human leptin has previously been shown to enhance cytokine production by murine peritoneal macrophages. In this paper we show that human leptin stimulates proliferation in a dose-dependent manner and functionally activates human circulating monocytes in vitro, by inducing the production of cytokines such as TNF-alpha and IL-6. Proliferation was assessed both by [3H]thymidine and bromodeoxyuridine incorporation at 48 h. We also checked the leptin stimulated monocyte expression of activation markers by flow cytometry: CD25, HLA-DR, CD38, CD71, CD11b, and CD11c expression increased after 72 h. Moreover, leptin increases the expression of the early activation marker CD69 in monocytes but not in lymphocytes. The stimulation produced by leptin is comparable to that produced by endotoxin [lipopolysaccharide (LPS)]. In addition, leptin can potentiate the stimulatory effect of LPS or PMA. Furthermore, we studied cytokine production (TNF-alpha and IL-6) simultaneously by flow cytometric detection of intracellular cytokines in the activated monocytes. Leptin produced a dose-dependent increase in the number of activated monocytes producing cytokines. These data indicate that leptin is a potent stimulatory hormone on human peripheral blood monocytes and suggest that it may have a role as a proinflammatory cytokine.
    Cellular Immunology 06/1999; 194(1):6-11. DOI:10.1006/cimm.1999.1490 · 1.87 Impact Factor
  • V Sánchez-Margalet · C González-Yanes · J Santos-Alvarez · S Najib
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin treatment of the membranes, suggesting the involvement of G proteins of the G alpha i/G alpha o family. The expression of these G alpha proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific G alpha protein activated by insulin stimulation. Anti-G alpha il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-G alpha o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with G alpha il,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin receptor signaling and provides some evidence of specific association and activation of G alpha il,2 protein by insulin. These findings suggest that G alpha il,2 proteins might be involved in insulin action.
    Cellular and Molecular Life Sciences CMLS 02/1999; 55(1):142-7. · 5.86 Impact Factor
  • V. Sánchez-Margalet · C. González-Yanes · J. Santos-Alvarez · S. Najib
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding of guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin treatment of the membranes, suggesting the involvement of G proteins of the Gα i/Gα o family. The expression of these Gα proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific Gα protein activated by insulin stimulation. Anti-Gα il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-Gα o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with Gα i1,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin receptor signaling and provides some evidence of specific association and activation of Gα i1,2 protein by insulin. These findings suggest that Gα i1,2 proteins might be involved in insulin action.
    Cellular and Molecular Life Sciences CMLS 12/1998; 55(1):142-147. DOI:10.1007/s000180050279 · 5.86 Impact Factor
  • J Santos-Alvarez · V Sánchez-Margalet
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreastatin (PST) receptors have been recently shown to mediate activation of phospholipase C (PLC) in rat liver membranes. There is evidence that the G protein that links pancreastatin receptor with PLC-beta is pertussis toxin-insensitive and belongs to the G(alpha)q family. Here, we have employed blocking antisera to sort out the specific PLC-beta isoform as well as the specific G(alpha) subunit activated by PST receptor in rat liver membranes. The presence of different PLC-beta isoforms was checked by immunoblot analysis. Only PLC-beta4 was not detected, whereas PLC-beta1, beta2 and beta3 were abundant in rat liver membranes. However, only anti-PLC-beta3 serum was able to block the PST receptor response. We also checked the expression of G(alpha)q and Galpha11 in rat liver membranes by immunoblot. Even though both isoforms were present. only anti-Galpha11 serum was able to block the PST receptor response. In order to check the specificity of the blocking antisera, we employed them to block the effect of ADP and thrombin stimulating PLC activity in platelet membranes, a system lacking Galpha11. Anti-G(alpha)q but not anti-Galpha11 sera were able to block the agonist stimulated PLC activity. These data suggest that PST receptor response is mediated by the activation of the beta3 isoform of PLC via Galpha11 protein stimulation in rat liver membranes.
    Molecular and Cellular Endocrinology 09/1998; 143(1-2):101-6. · 4.24 Impact Factor
  • José Santos-Álvarez · Vı́ctor Sánchez-Margalet
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreastatin (PST) receptors have been recently shown to mediate activation of phospholipase C (PLC) in rat liver membranes. There is evidence that the G protein that links pancreastatin receptor with PLC-β is pertussis toxin-insensitive and belongs to the Gαq family. Here, we have employed blocking antisera to sort out the specific PLC-β isoform as well as the specific Gα subunit activated by PST receptor in rat liver membranes. The presence of different PLC-β isoforms was checked by immunoblot analysis. Only PLC-β4 was not detected, whereas PLC-β1, β2 and β3 were abundant in rat liver membranes. However, only anti-PLC-β3 serum was able to block the PST receptor response. We also checked the expression of Gαq and Gα11 in rat liver membranes by immunoblot. Even though both isoforms were present, only anti-Gα11 serum was able to block the PST receptor response. In order to check the specificity of the blocking antisera, we employed them to block the effect of ADP and thrombin stimulating PLC activity in platelet membranes, a system lacking Gα11. Anti-Gαq but not anti-Gα11 sera were able to block the agonist stimulated PLC activity. These data suggest that PST receptor response is mediated by the activation of the β3 isoform of PLC via Gα11 protein stimulation in rat liver membranes.
    Molecular and Cellular Endocrinology 08/1998; 143(1-143):101-106. DOI:10.1016/S0303-7207(98)00137-3 · 4.24 Impact Factor