Localization of the somatostatin receptor SST2A in rat brain using a specific anti-peptide antibody

Department of Neurology, McGill University, Montréal, Québec, Canada.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/1996; 16(14):4468-78.
Source: PubMed


Biological actions of somatostatin are exerted via a family of receptors, for which five genes recently have been cloned. However, none of these receptor proteins has been visualized yet in the brain. In the present-study, the regional and cellular distribution of the somatostatin sst2A receptor was investigated via immunocytochemistry in the rat central nervous system by using an antibody generated against a unique sequence of the receptor protein. Specificity of the antiserum was demonstrated by immunoblot and immunocytochemistry on rat brain membranes and/or on cells transfected with cDNA encoding the different sst receptor subtypes. In rat brain sections, sst2A receptor immunoreactivity was concentrated either in perikarya and dendrites or in axon terminals distributed throughout the neuropil. Somatodendritic labeling was most prominent in the olfactory tubercle, layers II-III of the cerebral cortex, nucleus accumbens, pyramidal cells of CA1-CA2 subfields of the hippocampus, central and cortical amygdaloid nuclei, and locus coeruleus. Labeled terminals were detected mainly in the endopiriform nucleus, deep layers of the cortex, claustrum, substantia innominata, subiculum, basolateral amygdala, medial habenula, and periaqueductal gray. Electron microscopy confirmed the association of sst2A receptors with perikarya and dendrites in the former regions and with axon terminals in the latter. These results provide the first characterization of the cellular distribution of a somatostatin receptor in mammalian brain. The widespread distribution of the sst2A receptor in cerebral cortex and limbic structures suggests that it is involved in the transduction of both pre- and postsynaptic effects of somatostatin on cognition, learning, and memory.

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Available from: Gloria S Tannenbaum
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    • "Moreover, the PVN and surrounding areas are sites of action for the somatostatin agonist, octreotide to induce a drinking response in rats (Hajdu et al., 2003). There is also a dense expression of sst 2 receptors in the PVN with neuronal localization supporting both pre-and post-synaptic actions (Csaba et al., 2003; Dournaud et al., 1996). Moreover, the inhibitory action of somatostatin on GABA transmission is well documented (Kumar and Grant, 2010). "
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    ABSTRACT: Somatostatin was discovered four decades ago as hypothalamic factor inhibiting growth hormone release. Subsequently, somatostatin was found to be widely distributed throughout the brain and to exert pleiotropic actions via interaction with five somatostatin receptors (sst1-5) that are also widely expressed throughout the brain. Interestingly, in contrast to the predominantly inhibitory actions of peripheral somatostatin, the activation of brain sst2 signaling by intracerebroventricular injection of stable somatostatin agonists potently stimulates food intake and independently, drinking behavior in rodents. The orexigenic response involves downstream orexin-1, neuropeptide Y1 and μ receptor signaling while the dipsogenic effect is mediated through the activation of the brain angiotensin 1 receptor. Brain sst2 activation is part of mechanisms underlying the stimulation of feeding and more prominently water intake in the dark phase and is able to counteract the anorexic response to visceral stressors. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · May 2015 · Hormones and Behavior
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    • "However neuroanatomical circuitries that underlie the link between brain sst 2 receptor mediated orexigenic action of icv ODT8-SST [6] [7] and the recruitment of brain orexin neurons are still to be established. The sst 2 immunoreactivity is diffusely distributed throughout the hypothalamus [30] on both somatodendritic and axonic elements allowing transduction at the pre-and post-synaptic levels [31]. Our previous report [32] showed that the icv injection of ODT8-SST at the orexigenic dose used in the present study, induced Fos immunoreactivity mainly in the supraoptic nucleus and paraventricular nucleus unlike orexinproducing neurons located in caudal hypothalamus including the LHA, perifornical region or the dorsomedial nucleus in rats suggestive of an indirect action. "
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    ABSTRACT: Intracerebroventricular (icv) injection of the stable somatostatin pan-agonist, ODT8-SST induces a somatostatin 2 receptor (sst2) mediated robust feeding response that involves neuropeptide Y and opioid systems in rats. We investigated whether the orexigenic system driven by orexin also plays a role. Food and water intake after icv injection was measured concomitantly in non-fasted and non-water deprived rats during the light phase. In vehicle treated rats (100% DMSO, icv), ODT8-SST (1μg/rat, icv) significantly increased the 2-h food and water intake compared to icv vehicle plus saline (5.1±1.0g vs. 1.2±0.4g and 11.3±1.9mL vs. 2.5±1.2mL, respectively). The orexin-1 receptor antagonist, SB-334867 (16μg/rat, icv) completely inhibited the 2-h food and water intake induced by icv ODT8-SST. In contrast, the icv pretreatment with the selective somatostatin sst2 antagonist, S-406-028, established to block the orexigenic effect of icv ODT8-SST, did not modify the increased food and water intake induced by icv orexin-A (10.7μg/rat). These data indicate that orexin-1 receptor signaling system is part of the brain neurocircuitry contributing to the orexigenic and dipsogenic responses induced by icv ODT8-SST and that orexin-A stimulates food intake independently from brain sst2 activation.
    Full-text · Article · Jun 2014 · Neuroscience Letters
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    • "Somatostatin receptors sst2R, sst3R, and sst4R are highly expressed by hippocampal and entorhinal glutamatergic neurons (Breder et al., 1992; Dournaud et al., 1996; Schreff et al., 2000; Schulz et al., 2000). In the entorhinal termination zone, sst2R immunoreactivity was described on terminals (Dournaud et al., 1996), possibly mediating the presynaptic inhibitory effect of O-LM cells. The sst3R knockout mice show impaired object-recognition memories (Einstein et al., 2010). "
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    ABSTRACT: Neuropeptides acting on pre- and postsynaptic receptors are coreleased with GABA by interneurons including bistratified and O-LM cells, both expressing somatostatin but innervating segregated dendritic domains of pyramidal cells. Neuropeptide release requires high-frequency action potentials, but the firing patterns of most peptide/GABA-releasing interneurons during behavior are unknown. We show that behavioral and network states differentiate the activities of bistratified and O-LM cells in freely moving rats. Bistratified cells fire at higher rates during sleep than O-LM cells and, unlike O-LM cells, strongly increase spiking during sharp wave-associated ripples (SWRs). In contrast, O-LM interneurons decrease firing during sleep relative to awake states and are mostly inhibited during SWRs. During movement, both cell types fire cooperatively at the troughs of theta oscillations but with different frequencies. Somatostatin and GABA are differentially released to distinct dendritic zones of CA1 pyramidal cells during sleep and wakefulness to coordinate segregated glutamatergic inputs from entorhinal cortex and CA3.
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