Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-HT3 receptors may be present on primary afferent neurons containing substance P (SP), neurokinin A (NKA) or calcitonin gene-related peptide (CGRP). We investigated the release of SP-, NKA- and CGRP-immunoreactivities (IR) from rat spinal cord slices. Thirty mM potassium chloride caused an increased outflow of all three peptides, i.e. 140-190% of spontaneous release. This release was slightly enhanced in the presence of 3 x 10(-5) M 5-hydroxytryptamine (5-HT). In contrast, a significant inhibition of potassium-evoked, but not of basal NKA-IR and CGRP-IR release was observed when 10(-7) M BRL 43694 or ICS 205-930, two specific 5-HT3 receptor antagonists, were superfused together with 5-HT. In conclusion, 5-HT may facilitate the evoked release of peptides from central terminals of primary sensory neurons via 5-HT3 receptors.
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PMID:5-HT3 receptor antagonists inhibit sensory neuropeptide release from the rat spinal cord. 171 37

1. The aim of the present study was to determine the role of 5-HT3 receptors of the gastroprotective effect of salmon calcitonin (sCT) and sCT-induced changes in gastric, hepatic, brain and brainstem glutathione (GSH) and lipid-peroxidation (LP) levels in rats subjected to cold-immobilization stress. 2. Stress exposure resulted in ulcer formation and a decrease in GSH levels of the liver, brain and brainstem and an increase in gastric and hepatic LP (P < 0.05). 3. sCT prevented stress-induced gastric ulcer development (P < 0.01) and reversed the decrease in hepatic and brain GSH levels (P < 0.05). 4. In the present study, a 5-HT3 receptor antagonist, ICS 205,930 was used. Interestingly, the effect of the blocker on GSH and LP levels of the tissues studied was similar to those of sCT. 5. ICS 205,930 dose dependently reversed the anti-ulcer effect of sCT although it did not antagonize the effect of sCT on GSH and LP levels, but it seemed to show an additive interaction for brain and brainstem GSH and gastric LP levels with sCT.
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PMID:The role of 5-HT3 receptors in the anti-ulcer effect of calcitonin. 772 Oct 34

The use of high doses of cisplatin in treating cancers has been limited by two major adverse effects--emesis and peripheral neuropathies. The emesis has become largely controlled by the introduction of a new class of drugs--the 5-HT3 receptor antagonists. The current study was undertaken to determine if these drugs would also prevent cisplatin-induced neuropathy. We have used a developing rat as an animal model and determined the effects of cisplatin on morphology (loss of spinal cord calcitonin gene-related peptide (CGRP)-containing neurons) and behavior (gait abnormalities and pain perception). Rat pups from the age of 5 days were treated twice weekly for 4 weeks with cisplatin (1 mg/kg), the 5-HT3 antagonist MDL 72222 (3 mg/kg) or both. The animals were tested for pain perception (using tail-flick latencies) at 17 and 21 days of age and for a gait abnormality at 24 days of age. At 34 days of age, the animals were perfused and the lumbar region of the spinal cords stained immunocytochemically for CGRP. Our results show that cisplatin treatment resulted in a dramatic loss of CGRP neurons in the dorsal horn of the spinal cord and a corresponding increase in the animals' threshold for pain. In addition, the animals showed a pronounced gait abnormality, characterized by 'toeing-in'. Treatment with MDL 72222 not only failed to protect against the loss of CGRP neurons but also worsened the gait abnormalities seen after cisplatin treatment alone. These studies confirm and extend the list of morphological and functional adverse effects of cisplatin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A 5-HT3 receptor antagonist fails to prevent cisplatin-induced toxicity in immature rat spinal cord. 779 48

To elucidate the mechanism of antinociceptive effects of calcitonin, we investigated whether receptor antagonists for various neurotransmitter receptors alter the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice. Neither naloxone, an opioid receptor antagonist, phentolamine and benextramine, alpha-adrenoceptor antagonists, nor ritanserin, a 5-HT2A receptor antagonist, inhibited the calcitonin-induced anti-aversive effects. Pindolol and (--)-propranolol, non-selective antagonists of beta-adrenoceptors and 5-HT1 receptors, 1-(2-methoxyphenyl)-4-[4-(2-phethalimido) butyl]-piperazine hydrobromide (NAN-190), a 5-HT1A receptor antagonist, 3-tropanyl-3,5-dichlorobenzoate (MDL72222) and metoclopramide, 5-HT3 receptor antagonists, significantly inhibited the calcitonin-induced anti-aversive effects. (--)-Bicuculline, a GABAA receptor antagonist, phaclofen and 5-aminovaleric acid, GABAB receptor antagonists, also attenuated the calcitonin-induced anti-aversive effects. These results suggest that beta-adrenoceptor, 5-HT1A, 5-HT3, GABAA and GABAB receptors, but not alpha-adrenoceptor, opioid nor 5-HT2A receptors, are involved in the inhibitory effect of calcitonin on intrathecally injected N-methyl-D-aspartate-induced aversive behavior in mice.
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PMID:Neuronal mechanism of the inhibitory effect of calcitonin on N-methyl-D-aspartate-induced aversive behavior. 779 51

The contribution of calcitonin gene-related peptide (CGRP) to bilateral oedema formation in the rat hindpaw following an unilateral challenge with CGRP was investigated. Rats were injected into the left hindpaw with either saline, CGRP or a CGRP antagonist (CGRP8-37). All injections were given in a double blind fashion and in a volume of 100 microl. CGRP and CGRP8-37 were administered in concentrations of 75, 150 or 300 pmol. Volumes of the right and left hindpaw were measured every hour for 5 h by plethysmometry. Injection of CGRP 300 pmol into the left hindpaw resulted in a bilaterally increased hindpaw volume after 5 h as compared with the groups given saline. No changes were found in hindpaw volumes following the injection of either 75 or 150 pmol of CGRP or 75, 150 or 300 pmol of CGRP8-37 as compared with saline injection. To elucidate whether or not the bilateral oedema formation was related to a release of endogenous CGRP, microdialysis of the contralateral hindpaw was carried out, and concentrations of CGRP-like immunoreactivity (-LI) were determined by radioimmunoassay and high performance liquid chromatography. Injection of CGRP 300 pmol into the left hindpaw increased the release of CGRP-LI into the right hindpaw perfusate after 4 and 5 h. No changes in CGRP-LI were detected in the right hindpaw perfusate following challenge with saline or CGRP8-37. To study the contribution of the nervous system to the contralateral release of CGRP-LI, sciatic nerve ligated and intact sham-operated rats were used. Sciatic nerve ligation but not sham-operation on the non-injected side abolished the increased release of CGRP-LI following contralateral administration of CGRP 300 pmol. To study the spinal cord mechanisms resulting in the bilateral oedema formation following unilateral challenge with 300 pmol of CGRP, intrathecal pretreatment with either 10 nmol bicuculline (GABA(A) receptor antagonist) or 10 nmol CGRP8-37 was carried out. Bicuculline but not CGRP8-37 abolished the bilateral oedema formation induced by CGRP 300 pmol. In order to study the mechanisms by which administration of CGRP 300 pmol induces oedema, CGRP 300 pmol was administered concomitantly with either 300 pmol of CGRP8-37 (CGRP receptor antagonist), or 3 nmol of promethazine (H1 receptor antagonist), or 3 nmol of s(-)-propranolol (5-HT1 receptor antagonist), or 3 nmol of cyproheptadine (5-HT2 receptor antagonist) or 3 nmol of ICS 205-930 (5-HT3 receptor antagonist). Oedema formation was measured at 1, 5, 7 and 24 h. Injection of CGRP 300 pmol into the left hindpaw induced a bilateral oedema formation which was still significant at 24 h. Concomitant administration of either CGRP8-37, ICS 205-920 or cyproheptadine blocked the oedema formation at 24 h. No effect on oedema formation was found when CGRP 300 pmol was co-administered with either promethazine or s(-)-propranolol (H1 and 5-HT1 receptor antagonists, respectively). The results of the present study show that both the nervous system and local inflammatory processes contribute to bilateral hindpaw oedema formation following unilateral challenge with CGRP 300 pmol. Our results indicate that endogenous release of CGRP following inflammatory response may play an important role in inducing oedema formation.
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PMID:Unilateral injection of calcitonin gene-related peptide (CGRP) induces bilateral oedema formation and release of CGRP-like immunoreactivity in the rat hindpaw. 986 61

We investigated the mechanisms of 5-HT-induced tachycardia, which we reported previously to be triggered by 5-HT3 receptor stimulation, in the isolated guinea pig atrium in comparison with that induced by isoproterenol and histamine. We found that 5-HT-induced tachycardia was completely inhibited by ruthenium red. 5-HT-induced tachycardia was reduced in the capsaicin pre-treated atrium as well as in the presence of capsaicin. The effects of isoproterenol and histamine were not affected by ruthenium red or capsaicin treatment. Furthermore, 5-HT-induced tachycardia was found to be potentiated by thiorphan, an inhibitor of peptide degeneration. Calcitonin gene-related peptide (CGRP) (1-37), a full agonist of CGRP1-like receptors, was found to act selectively as a potent stimulator of chronotropic action. CGRP (8-37), an antagonist of CGRP1-type receptors, inhibited 5-HT-induced tachycardia as well as effects induced by CGRP (1-37). The observation that tetrodotoxin failed to affect 5-HT-induced tachycardia excluded the involvement of 5-hydroxytryptaminergic interneurons. Thus, we confirmed that the mechanism of 5-HT-induced tachycardia is distinct from that induced by isoproterenol and histamine. In conclusion, the activation of 5-HT3 receptors on the sensory nerve terminals brought about ruthenium red-sensitive Ca2+ influx and resulted in the release of CGRP from capsaicin-sensitive stores, and then CGRP stimulated CGRP1-like receptors to produce 5-HT-induced tachycardia.
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PMID:5-HT-induced, 5-HT3 receptor-mediated, and ruthenium red- and capsaicin-sensitive positive chronotropic effects in the isolated guinea pig atrium. 1218 29

5-Hydroxytryptamine (5-HT) activates colonic splanchnic afferents, a mechanism by which it has been implicated in generating symptoms in postinfectious and postinflammatory states in humans. Here we compared mechanisms of colonic afferent activation by 5-HT and mechanical stimuli in normal and inflamed rat colon, and after recovery from inflammation. Colonic inflammation was induced in rats by dextran sulphate sodium. Single-fibre recordings of colonic lumbar splanchnic afferents revealed that 58% of endings responded to 5-HT (10(-4) m) in controls, 88% in acute inflammation (P<0.05) and 75% after 21 days recovery (P < 0.05 versus control). Maximal responses to 5-HT were also larger, and the estimated EC50 was reduced from 3.2 x 10(-6) to 8 x 10(-7) m in acute inflammation and recovered to 2 x 10(-6) m after recovery. Responsiveness to mechanical stimulation was unaffected. 5-HT3 receptor antagonism with alosetron reduced responses to 5-HT in controls but not during inflammation. Responses to the mast cell degranulator 48/80 mimicked those to 5-HT in inflamed tissue but not in controls, and more 5-HT-containing mast cells were seen close to calcitonin gene-related peptide-containing fibres in inflamed serosa. We conclude that colonic serosal and mesenteric endings exhibit increased sensitivity to 5-HT in inflammation, with both an increase in proportion of responders and an increase in sensitivity, which is maintained after healing of inflammation. This is associated with alterations in the roles of 5-HT3 receptors and mast cells.
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PMID:Increased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery. 1713 6