Somatostatin sst2 receptor–mediated inhibition of mesenteric afferent nerves of the jejunum in the anesthetized rat

Booth, Charlotte E.; Kirkup, Anthony J.; Hicks, Gareth A.; Humphrey, P. P. A.; Grundy, David

doi:10.1053/gast.2001.26335

Cited by 69 publications

(67 citation statements)

References 30 publications

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“…In agreement with previous results [15], CYN-154806 antagonizes sst 2 receptor action on [Ca 2+ ] i depending on ligand concentration, thus suggesting the surmountable nature of CYN-154806 blockade [31]. CYN-154806 displays antagonistic properties at sst 2 receptors in different experimental models, including GC cells [32]; for references, see 15]. …”

Section: Discussionsupporting

confidence: 90%

Inhibitory Control of Growth Hormone Secretion by Somatostatin in Rat Pituitary GC Cells: sst2 but Not sst1 Receptors Are Coupled to Inhibition of Single-Cell Intracellular Free Calcium Concentrations

Cervia

Petrucci²,

Bluet-Pajot³

et al. 2002

Neuroendocrinology

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Rat pituitary tumor cells (GC cells) exhibit spontaneous oscillations of intracellular free calcium concentration ([Ca²⁺]_i) that allow continuous release of growth hormone (GH). Of the somatostatin (SRIH) receptor subtypes (sst receptors) mediating SRIH action, sst₁ and sst₂ receptors are highly expressed by GC cell membranes. In the present study, the effects of sst₁ or sst₂ receptor activation on single-cell [Ca²⁺]_i were investigated in GC cells by confocal fluorescence microscopy. In addition, the effects of sst₁ or sst₂ receptor activation on GH secretion were also studied. Our results demonstrate that SRIH decreases [Ca²⁺]_i baseline and almost completely blocks Ca²⁺ transients through activation of sst₂ but not of sst₁ receptors. In contrast, SRIH effectively inhibits GH secretion through activation of both sst₁ and sst₂ receptors. Blocking Ca²⁺ transients is less efficient than SRIH to inhibit GH release. The cyclic octapeptide, CYN-154806, antagonizes sst₂ receptors at [Ca²⁺]_i since it abolishes the sst₂ receptor-mediated inhibition of [Ca²⁺]_i without affecting single-cell Ca²⁺ signals. On the other hand, CYN-154806 alone potently inhibits GH secretion through the involvement of pertussis toxin-sensitive G proteins. In conclusion, the present results demonstrate that SRIH inhibition of GH release in GC cells involves mechanisms either dependent or independent on SRIH modulation of [Ca²⁺]_i. The implications of CYN-154806 inhibition of GH secretion are discussed.

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Section: Discussionsupporting

confidence: 90%

Inhibitory Control of Growth Hormone Secretion by Somatostatin in Rat Pituitary GC Cells: sst2 but Not sst1 Receptors Are Coupled to Inhibition of Single-Cell Intracellular Free Calcium Concentrations

Cervia

Petrucci²,

Bluet-Pajot³

et al. 2002

Neuroendocrinology

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“…Electrophysiological recordings from afferent neurons in anesthetized animals show that each contraction or distention in the gut stimulates afferent signaling whose intensity is proportional to the stimulus amplitude (8,20,61). It is likely that, because of their large amplitude and long duration, the GMCs trigger high-threshold sensory fibers, whereas the RPCs trigger low-threshold fibers (11).…”

Section: Pseudoaffective Responses To Balloon Distension and Gmcsmentioning

confidence: 99%

Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain

Sarna¹

2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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We investigated whether strong compression of an intestinal segment by giant migrating contractions (GMCs) initiates pseudoaffective signals from the gut, similar to those initiated by its distension with a balloon. The experiments were performed on conscious dogs by using close intra-arterial infusions of test substances that affect the receptors only in the infused segment. The stimulation of GMCs by close intra-arterial infusion of CGRP or distension of an intestinal segment by balloon increased the heart rate; the increase in heart rate was greater when the balloon distension and GMCs occurred concurrently in separate intestinal segments. The suppression of contractility in the distended segment blocked the increase in heart rate. By contrast, the stimulation of rhythmic phasic contractions (RPCs) or their spontaneous occurrence did not increase the heart rate. The occurrence of GMCs as well as intestinal distension also produced descending inhibition. The descending inhibition was blocked by the inhibition of nitric oxide synthase, but it was unaffected by the inhibition of adenylyl cyclase, purinergic receptors P2X and P2Y, and muscarinic receptors M(1) and M(2). The synaptic transmission for descending inhibition was mediated primarily by nicotinic receptors and activation of nitric oxide synthase. It was unaffected by the inhibition of tachykinin receptors NK(1), NK(2), and NK(3); serotonin receptors 5-HT(1A), 5-HT(2)/5-HT(1C), 5-HT(3), and 5-HT(4); and muscarinic receptors. Our findings show that GMCs, but not RPCs, initiate pseudoaffective signals from the gut. In the presence of visceral hypersensitivity or impaired descending inhibition, the GMCs may become a noxious stimulus.

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“…Among these, somatostatin has been known to inhibit basal and stimulated chloride secretion in colonocytes, both by a direct action on the colonocytes and by inhibiting other enteric neurons (Mckeen et al, 1995;Warhurst et al, 1996;Cooke et al, 2003). Somatostatin is present in about 15-20% of secretomotor neurons in the submucosal plexus (Furness, 2000) and also in D cells of the gastric and duodenal epithelia (Booth et al, 2001). Once released, somatostatin is believed to function as an inhibitory neurotransmitter to inhibit colonic secretion by binding to the sst 2 receptors on epithelial cells to reduce intracellular cAMP (Mckeen et al, 1995;Warhurst et al, 1996) and/or by hyperpolarizing the membrane potential and suppressing excitability of secretomotor neurons in the submucosal plexus (Shen and Surprenant, 1993;Liu et al, 2000) ( Figure 8A).…”

Section: Submucosal 5-ht3 Receptor-mediated Inhibition Of Colonic Ionmentioning

confidence: 99%

Activation of submucosal 5‐HT₃ receptors elicits a somatostatin‐dependent inhibition of ion secretion in rat colon

Yang

Liu

Zheng

et al. 2010

British J Pharmacology

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Background and purpose: 5-Hydroxytryptamine (5-HT) is a key regulator of the gastrointestinal system and we have shown that submucosal neuronal 5-HT3 receptors exerted a novel inhibitory effect on colonic ion transport. The aim of the present study was to investigate the precise mechanism(s) underlying this inhibitory effect. Experimental approach: Mucosa/submucosa or mucosa-only preparations from rat distal colon were mounted in Ussing chambers for measurement of short-circuit current (Isc) as an indicator of ion secretion. Somatostatin release was determined with radioimmunoassay. Intracellular cAMP content was measured with enzyme-linked immunoadsorbent assay (ELISA). Immunohistochemical techniques were used to study the expression of 5-HT3 receptors, somatostatin and somatostatin receptors in colonic tissue. Key results: In rat distal colonic mucosa/submucosa preparations, pretreatment with 5-HT3 receptor antagonists enhanced 5-HT-induced increases in Isc. However, in mucosa-only preparations without retained neural elements, pretreatment with 5-HT3 receptor antagonists inhibited 5-HT-induced DIsc. Pretreatment with a somatostatin-2 (sst2) receptor antagonist in mucosa/ submucosa preparations augmented 5-HT-induced DIsc. Combination of sst2 and 5-HT3 receptor antagonists did not cause further enhancement of 5-HT-induced DIsc. Moreover, both sst2 and 5-HT3 receptor antagonists enhanced 5-HT-induced increase in intracellular cAMP concentration in the mucosa/submucosa preparations. 5-HT released somatostatin from rat colonic mucosa/ submucosa preparations, an effect prevented by pretreatment with 5-HT3 receptor antagonists. Immunohistochemical staining demonstrated the presence of 5-HT3 receptors on submucosal somatostatin neurons and of sst2 receptors on colonic mucosa. Conclusion and implications: Activation of neuronal 5-HT3 receptors in the submucosal plexus of rat colon suppressed 5-HT-induced ion secretion by releasing somatostatin from submucosal neurons.

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Somatostatin sst2 receptor–mediated inhibition of mesenteric afferent nerves of the jejunum in the anesthetized rat

Cited by 69 publications

References 30 publications

Inhibitory Control of Growth Hormone Secretion by Somatostatin in Rat Pituitary GC Cells: sst<sub>2</sub> but Not sst<sub>1</sub> Receptors Are Coupled to Inhibition of Single-Cell Intracellular Free Calcium Concentrations

Inhibitory Control of Growth Hormone Secretion by Somatostatin in Rat Pituitary GC Cells: sst<sub>2</sub> but Not sst<sub>1</sub> Receptors Are Coupled to Inhibition of Single-Cell Intracellular Free Calcium Concentrations

Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain

Activation of submucosal 5‐HT₃ receptors elicits a somatostatin‐dependent inhibition of ion secretion in rat colon

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Somatostatin sst2 receptor–mediated inhibition of mesenteric afferent nerves of the jejunum in the anesthetized rat

Cited by 69 publications

References 30 publications

Inhibitory Control of Growth Hormone Secretion by Somatostatin in Rat Pituitary GC Cells: sst<sub>2</sub> but Not sst<sub>1</sub> Receptors Are Coupled to Inhibition of Single-Cell Intracellular Free Calcium Concentrations

Inhibitory Control of Growth Hormone Secretion by Somatostatin in Rat Pituitary GC Cells: sst<sub>2</sub> but Not sst<sub>1</sub> Receptors Are Coupled to Inhibition of Single-Cell Intracellular Free Calcium Concentrations

Enteric descending and afferent neural signaling stimulated by giant migrating contractions: essential contributing factors to visceral pain

Activation of submucosal 5‐HT3 receptors elicits a somatostatin‐dependent inhibition of ion secretion in rat colon

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Activation of submucosal 5‐HT₃ receptors elicits a somatostatin‐dependent inhibition of ion secretion in rat colon