Role of 5-HT1-like receptors in the increase in intragastric pressure induced by 5-hydroxytryptamine in the rat.
The study concerned the effects of 5-hydroxytryptamine (5-HT) on intragastric pressure in bilaterally vagotomized spinal rats. Intravenous (i.v.) bolus injections of 5-HT (2.5, 5.0 and 10 micrograms/kg) produced dose-dependent increases in intragastric pressure; these effects were not modified by atropine (up to 0.2 mg/kg) or mepyramine (1 mg/kg), but were blocked by the mixed 5-HT1-like and 5-HT2 receptor antagonists, methiothepin (0.1, 0.3 and 0.5 mg/kg i.v.) and methysergide (0.5, 1 and 2.5 mg/kg i.v.). However, metergoline (0.5, 1 and 2 mg/kg i.v.) did not markedly modify this effect of 5-HT; only the response induced by 5 micrograms/kg 5-HT was significantly antagonized by the highest dose of metergoline. In contrast, neither the 5-HT2 receptor antagonist, ketanserin (0.5, 1 and 1.5 mg/kg i.v.), nor the 5-HT3 receptor antagonist, ICS 205-930 (0.5, 1 and 3 mg/kg i.v.), influenced the 5-HT-induced increase in intragastric pressure. In addition, 5-carboxamidotryptamine (25, 50 and 100 micrograms/kg i.v.) and RU 24969 (50, 100 and 200 micrograms/kg i.v.) mimicked the aforementioned effects of 5-HT but were weaker than 5-HT. These data suggest that the 5-HT-induced increase in intragastric pressure in the spinal and bilaterally vagotomized rat is mediated by an atypical 5-HT1-like receptor, which, based on the low agonist potency of 5-carboxamidotryptamine and RU 24969 and the resistance to blockade by metergoline, does not seem to correspond to either the 5-HT1A, 5-HT1B, 5-HT1C or the 5-HT1D receptor subtypes.
Dhasmana
K M
KM
Department of Anaesthesiology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Netherlands.
Villalón
C M
CM
Zhu
Y N
YN
Tadipatri
S
S
Saxena
P R
PR
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D011312:Pressure; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects* / Q000502:physiology; D000077526:Tropisetron
D002395:Catecholamines; D007211:Indoles; D011985:Receptors, Serotonin; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D008719:Methiothepin; D000077526:Tropisetron; D001285:Atropine; C047087:5-carboxamidotryptamine; D007650:Ketanserin; D011738:Pyrilamine; D008784:Methysergide