Pertussis toxin attenuates 5-hydroxytryptamine1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes.
The inhibition of forskolin-stimulated adenylate cyclase activity by 5-hydroxytryptamine (5-HT) receptor agonists was measured in rat hippocampal membranes isolated from animals treated with vehicle or islet-activating protein (IAP; pertussis toxin). In vehicle-treated animals, 5-HT, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, and gepirone were potent in inhibiting forskolin-stimulated adenylate cyclase activity with EC50 values of 60, 76, 376, and 530 nM, respectively. IAP treatment reduced by 30-55% the 5-HT1A agonist inhibition of adenylate cyclase activity via 5-HT1A receptors. The data indicate that the inhibitory guanine nucleotide-binding protein or Go (a similar GTP-binding protein of unknown function purified from brain) mediates the 5-HT1A agonist inhibition of hippocampal adenylate cyclase.
Okada
F
F
Health Administration Center Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Tokumitsu
Y
Y
Nomura
Y
Y
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008970:Molecular Weight; D037342:Pertussis Toxin; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D008565:Membrane Proteins; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C039979:gepirone; D002065:Buspirone