BRL 24924: a potent agonist at a non-classical 5-HT receptor positively coupled with adenylate cyclase in colliculi neurons.
A non-classical 5-hydroxytryptamine (5-HT) receptor that we have previously proposed to call 5-HT4 and which mediates stimulation of adenylate cyclase activity in mouse embryo colliculi neurons in primary culture was also stimulated by substituted benzamide derivatives such as metoclopramide and BRL 24924 ([ (+/-)-(endo)]-4-amino-5-chloro-2-methoxy-N-(1-azabicyclo-[3.3.1]-non- 4-yl)-benzamide hydrochloride). The non-additivity of the effects of 5-HT and BRL 24924 on cAMP formation and the inhibition by ICS 205 930, a potent 5-HT3 antagonist, suggest that 5-HT and BRL 24924 act on the same receptor. In light of these results, we think that a similarity may exist between the non-classical 5-HT receptor, coupled with an adenylate cyclase in colliculi neurons, and the non-classical 5-HT receptor, involved in gastric and ileum motility which is specifically stimulated by substituted benzamide derivatives in the same order of potency (metoclopramide, BRL 24924).
Dumuis
A
A
Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Montpellier, France.
Sebben
M
M
Bockaert
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004622:Embryo, Mammalian; D005260:Female; D007211:Indoles / Q000494:pharmacology; D008787:Metoclopramide / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D007211:Indoles; D012702:Serotonin Antagonists; D000077526:Tropisetron; C053006:renzapride; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D008787:Metoclopramide