Islet-activating protein discriminates between different inhibitors of thyroidal cyclic AMP system.
TSH-induced cyclic AMP accumulation in dog thyroid slices is inhibited by norepinephrine through an alpha 2-adrenergic receptor, by carbamylcholine through a muscarinic cholinergic receptor, and by iodide. The inhibitory effect of iodide bears on the adenylate cyclase, but the exact mechanism of its action is still unknown. It is known that norepinephrine acts through activation of the Ni subunit of the cyclase, and that carbamylcholine, activating a phosphodiesterase, acts independently of Ni. IAP (islet-activating protein) has been shown to inactivate the Ni subunit. We studied the effect of IAP on the inhibitory action of iodide, norepinephrine, and carbamylcholine on cyclic AMP accumulation in TSH-stimulated thyroid slices. Incubations of 15 or 22 h, and relatively high concentrations of IAP (250 ng/ml) were necessary to demonstrate an effect of IAP on thyroid slices. We report here that, under those conditions, inhibition of cyclic AMP accumulation by norepinephrine, but not by carbamylcholine or iodide, was suppressed by IAP treatment. These results indicate that the cyclase inhibition by iodide, is either not mediated by Ni, or if mediated by Ni, involves a mode of regulation of this coupling protein that is different from that by which the other 'Ni-mediated' inhibitory hormones act on the enzyme.
Cochaux
P
P
Van Sande
J
J
Dumont
J E
JE
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004285:Dogs; D007454:Iodides / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D001427:Bacterial Toxins; D007454:Iodides; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D002217:Carbachol; D013972:Thyrotropin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D009638:Norepinephrine