Neuroendocrine regulatory peptide-1 and neuroendocrine regulatory peptide-2 influence differentially feeding and penile erection in male rats: Sites of action in the brain
Bernard B Brodie Department of Neuroscience and Centre of Excellence for the Neurobiology of Addictions, University of Cagliari, and Institute of Neuroscience, National Research Council, Cagliari Section, 09042 Monserrato, Cagliari, Italy.Regulatory Peptides (Impact Factor: 1.83). 05/2012; 177(1-3):46-52. DOI: 10.1016/j.regpep.2012.04.007
The effect of NERP-1 and NERP-2, two recently discovered VGF-derived peptides, on feeding and penile erection was studied after injection into the lateral ventricles, the lateral hypothalamus, the arcuate nucleus or the paraventricular nucleus of the hypothalamus. NERP-2 (1-5 nmol), but not NERP-1 (2-4 nmol), increased feeding in a dose-dependent manner when injected into the lateral ventricles or bilaterally into the lateral hypothalamus but not into the arcuate or the paraventricular nucleus. The effect of NERP-2 given into the lateral ventricles was found in the first, but not in the second 60 min after treatment, and was antagonized by SB-408124, an orexin-1 receptor antagonist given into the lateral ventricles or the arcuate nucleus, but not into the paraventricular nucleus. However, SB-408124 was unable to reduce NERP-2-induced feeding when injected bilaterally into the lateral hypothalamus before NERP-2 given also bilaterally into the lateral hypothalamus. In contrast, NERP-1, but not NERP-2, induced penile erection in a dose-dependent manner when injected into the lateral ventricles or the arcuate nucleus, but not into the paraventricular nucleus or the lateral hypothalamus. The pro-erectile effect of NERP-1 was not prevented by the prior injection of d(CH(2))(5)Tyr (Me)(2)-Orn(8)-oxytocin or SB-408124 into the lateral ventricles. The present results suggest that while NERP-2 facilitates feeding by acting in the lateral hypothalamus, possibly by increasing orexin activity in the arcuate nucleus, NERP-1 facilitates penile erection by acting in the arcuate nucleus with a mechanism not related to orexin or oxytocin.
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ABSTRACT: Of the numerous neuropeptides identified in the central nervous system, only a few are involved in the control of sexual behavior. Among these, the most studied are oxytocin, adrenocorticotropin, α-melanocyte stimulating hormone and opioid peptides. While opioid peptides inhibit sexual performance, the others facilitate sexual behavior in most of the species studied so far (rats, mice, monkeys and humans). However, evidence for a sexual role of gonadotropin-releasing hormone, corticotropin releasing factor, neuropeptide Y, galanin and galanin-like peptide, cholecystokinin, substance P, vasoactive intestinal peptide, vasopressin, angiotensin II, hypocretins/orexins and VGF-derived peptides are also available. Corticotropin releasing factor, neuropeptide Y, cholecystokinin, vasopressin and angiotensin II inhibit, while substance P, vasoactive intestinal peptide, hypocretins/orexins and some VGF-derived peptide facilitate sexual behavior. Neuropeptides influence sexual behavior by acting mainly in the hypothalamic nuclei (i.e., lateral hypothalamus, paraventricular nucleus, ventromedial nucleus, arcuate nucleus), in the medial preoptic area and in the spinal cord. However, it is often unclear whether neuropeptides influence the anticipatory phase (sexual arousal and/or motivation) or the consummatory phase (performance) of sexual behavior, except in a few cases (e.g., opioid peptides and oxytocin). Unfortunately, scarce information has been added in the last 15 years on the neural mechanisms by which neuropeptides influence sexual behavior, most studied neuropeptides apart. This may be due to a decreased interest of researchers on neuropeptides and sexual behavior or on sexual behavior in general. Such a decrease may be related to the discovery of orally effective, locally acting type V phosphodiesterase inhibitors for the therapy of erectile dysfunction.
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ABSTRACT: Catecholamines (CAs) and granin peptides are costored in dense-core vesicles within the chromaffin cells of the adrenal medulla and in other endocrine organs and neurons. Granins play a major functional and structural role in chromaffin cells but are ubiquitous proteins, which are present also in secretory cells of the nervous, endocrine, and immune systems, where they regulate a number of cellular functions. Furthermore, recent studies also demonstrate that granin-derived peptides can functionally interact with CA to modulate key physiological functions such as lipolysis and blood pressure. In this chapter, we will provide a brief update on the interaction between CA and granins at the cellular and organ levels. We will first discuss recent data on the regulation of exocytosis of CA and peptides from the chromaffin cells by the sympathetic nervous system with a specific reference to the prominent role played by splanchnic nerve-derived pituitary adenylate cyclase-activating peptide (PACAP). Secondly, we will discuss the role of granins in the storage and regulation of exocytosis in large dense-core vesicles. Finally, we will provide an up-to-date review of the roles played by two granin-derived peptides, the chromogranin A-derived peptide catestatin and the VGF-derived peptide TLQP-21, on lipolysis and obesity. In conclusion, the knowledge gathered from recent findings on the role played by proteins/peptides in the sympathetic/target cell synapses, discussed in this chapter, would contribute to and provide novel mechanistic support for an increased appreciation of the physiological role of CA in human pathophysiology.
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ABSTRACT: Targeted deletion of VGF, a secreted neuronal and endocrine peptide precursor, produces lean, hypermetabolic and infertile mice that are resistant to diet-, lesion-, and genetically-induced obesity and diabetes. Previous studies suggest that VGF controls energy expenditure, fat storage, and lipolysis, while VGF C-terminal peptides also regulate reproductive behavior and glucose homeostasis. To assess the functional equivalence of human VGF1-615 (hVGF) and mouse VGF1-617 (mVGF), and to elucidate the function of the VGF C-terminal region in the regulation of energy balance and susceptibility to obesity, we generated humanized VGF knockin mouse models expressing full-length hVGF or a C-terminally deleted human VGF1-524 (hSNP), encoded by a single nucleotide polymorphism (SNP rs35400704). We show that homozygous male and female hVGFand hSNPmice are fertile. hVGF female mice had significantly increased body weight compared to wild typemice, while hSNPmice have reduced adiposity, increased activity- and non-activity related energy expenditure (EE) and improved glucose tolerance indicating that VGF C-terminal peptides are not required for reproductive function, but one or more specific VGF C-terminal peptides are likely to be critical regulators of energy expenditure. Taken together, our results suggest that human and mouse VGF proteins are largely functionally conserved, but that species-specific differences in VGF peptide function, perhaps a result of known differences in receptor binding affinity, likely alter the metabolic phenotype of hVGF compared to mVGF mice, and in hSNP mice in which several C-terminal VGF peptides are ablated, results in significantly increased activity- and non-activity related EE.
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