Islet-activating protein inhibits the beta-adrenergic receptor facilitation elicited by gamma-aminobutyric acidB receptors.
gamma-Aminobutyric acidB (GABAB) receptor recognition sites that inhibit cyclic AMP formation, open potassium channels, and close calcium channels are coupled to these effector systems by guanine nucleotide binding proteins (G proteins). These G proteins are ADP-ribosylated by islet-activating protein (IAP), also known as pertussis toxin. This process prevents receptor coupling to these G proteins. In slices of cerebral cortex and hippocampus from rat, stimulation of GABAB receptors with baclofen, a receptor agonist, also potentiates the accumulation of cyclic AMP stimulated by beta-adrenergic agonists. It was unknown whether those GABAB receptors that potentiate the beta-adrenergic response were also sensitive to IAP. IAP was injected intracerebroventricularly into rats to ADP-ribosylate IAP-sensitive G proteins. Four days after the IAP injection, 38% and 52% of these G proteins from cerebral cortex and hippocampus, respectively, were ADP-ribosylated by the IAP injection. In slices of both structures prepared from IAP-treated rats, the GABAB receptor-mediated potentiation of the beta-adrenergic receptor response was attenuated. Thus, many GABAB receptor-mediated responses are coupled to IAP-sensitive G proteins.
Wojcik
W J
WJ
Fidia Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington D.C. 20007.
Ulivi
M
M
Paez
X
X
Costa
E
E
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004357:Drug Synergism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D001418:Baclofen; D007545:Isoproterenol