Inhibitory effect of 5-hydroxytryptamine on rat stomach fundus: mediated indirectly by activation of noradrenaline release.
Biphasic cumulative concentration-response curves to 5-hydroxytryptamine (5-HT) and alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT) using rat stomach fundus in the presence of 50 microM pargyline suggested two sites of interaction (high and low affinity). The order of agonist potencies of 5-HT agonists for the high-affinity (contractile) response confirmed reports of a strong correlation of the 5-HT2B (contractile) receptor on fundus with reported rat brain (radioligand binding) pKd values at the 5-HT2C receptor (r = 0.94, b = 0.93 P < 0.01). 1(1-Naphthyl)-piperazine and ketanserin antagonized the high-affinity responses. The order of potencies for the low affinity (inhibitory) response was: alpha-Me-5-HT > 5-HT. Preincubation with mianserin or S-(-)propranolol, pretreatment with reserpine and removal of the mucosa layer resulted in amplification of the contractile effects and disappearance or reversal of the inhibitory effects of 5-HT. Activation of a second receptor site inducing catecholamine release may explain this effect of 5-HT on rat stomach fundus.
Béjar
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Physiology-Pharmacology Department, School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA.
Malone
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D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005748:Gastric Fundus / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D009638:Norepinephrine