Inhibition of hormone-sensitive adenyl cyclase by phenothiazines.
Chlorpromazine (3 x 10(-4)M) prevents the stimulation of adenyl cyclase activity in thyroid membranes produced by thyrotropin and prostaglandin, ACTH stimulation of adenyl cyclase in adrenal tissue, and glucagon- and epinephrine-stimulation of adenyl cyclase activity in liver. Baseline activity is unaffected. Parathyroid hormone stimulation of kidney preparations was not inhibited under these conditions. At chlorpromazine concentrations >3 x 10(-4)M F(-)-stimulated cyclase activity of thyroid and adrenal tissue was increased. Other phenothiazines, trifluoperazine, and prochlorperazine, have similar effects on thyrotropin and F(-)-stimulated cyclase activity of thyroid. Na(+)- K(+)-dependent ATPase of thyroid is also inhibited by chlorpromazine. Since thymol causes a similar dissociation of hormone- and F(-)-stimulated adenyl cyclase, it is concluded that the surface properties of these agents best account for their effects on adenyl cyclase.
D000227:Adenine Nucleotides; D000067956:Adenylyl Cyclase Inhibitors; D000311:Adrenal Glands / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D002746:Chlorpromazine / Q000494:pharmacology; D004791:Enzyme Inhibitors; D004837:Epinephrine / Q000037:antagonists & inhibitors; D005459:Fluorides / Q000494:pharmacology; D005934:Glucagon / Q000037:antagonists & inhibitors; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D010640:Phenothiazines / Q000494:pharmacology*; D010908:Pituitary Hormones, Anterior / Q000037:antagonists & inhibitors*; D011346:Prochlorperazine / Q000494:pharmacology; D011448:Prostaglandin Antagonists; D013268:Stimulation, Chemical; D013943:Thymol / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000201:enzymology*; D013972:Thyrotropin / Q000037:antagonists & inhibitors; D014268:Trifluoperazine / Q000494:pharmacology
D000227:Adenine Nucleotides; D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D010640:Phenothiazines; D010908:Pituitary Hormones, Anterior; D011448:Prostaglandin Antagonists; D014268:Trifluoperazine; D013943:Thymol; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin; D005934:Glucagon; D005459:Fluorides; D002746:Chlorpromazine; D011346:Prochlorperazine; D004837:Epinephrine