Pharmacological characterization of 5-hydroxytryptamine4(5-HT4) receptors positively coupled to adenylate cyclase in adult guinea pig hippocampal membranes: effect of substituted benzamide derivatives.
Adult guinea pig hippocampal membranes contain two 5-hydroxytryptamine (5-HT) receptors positively coupled with an adenylate cyclase. One is a typical 5-HT1A receptor and the second is a nonclassical 5-HT receptor that we previously proposed to call 5-HT4. Here, we show that 4-amino-5-chlor-2-methoxy-benzamide derivatives are agonists of 5-HT4 receptors in guinea pig hippocampal membranes. Their effects on the adenylate cyclase of these membranes are not additive with those of 5-HT but are additive with those of RU 24969, a typical 5-HT1 agonist. The effects of benzamides, as well as those of 5-HT, on 5-HT4 receptors are not blocked by 5-HT1, 5-HT2, or 5-HT3 antagonists except ICS 205 903, which does so with a low affinity (1 microM). The potency of benzamides (cisapride greater than BRL 24924 greater than zacopride greater than BRL 20627 greater than metoclopramide) is similar to their effect of 5-HT4 receptors positively coupled with an adenylate cyclase of fetal mouse colliculi neurons.
Bockaert
J
J
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Sebben
M
M
Dumuis
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction; D013134:Spiperone / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000077526:Tropisetron
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D011985:Receptors, Serotonin; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D013134:Spiperone; D000077526:Tropisetron; C053006:renzapride; C055971:zacopride; D000262:Adenylyl Cyclases