Dissociation by cooling of hormone and cholera toxin activation of adenylate cyclase in intact cells.
Cholera toxin, through adenylate cyclase activation reproduced cyclic AMP-mediated effects of thyroid-stimulating hormone (TSH) in dog thyroid slices, i.e. protein iodination, [1-14C]glucose-oxidation and hormone secretion. Iodide and carbamylcholine decreased the cyclic AMP accumulation induced by cholera toxin as well as by TSH, which supports the hypothesis of an action of these agents beyond the steps of hormone-receptor and receptor-adenylate cyclase interaction. Cooling to 20 degrees C did not impair the TSH induced cyclic AMP accumulation in thyroid slices, but completely suppressed the cholera toxin effect. This observation has been extended to other hormones and target tissues, such as the parathyroid hormone (PTH) (kidney cortex), adrenocorticotropic hormone (ACTH) (adrenal cortex) and luteinizing hormone (LH) (ovary systems). As in thyroid, cooling dissociated the cholera toxin and hormonal effects on cyclic AMP accumulation. In homogenate, cooling decreased cyclic AMP generation in the presence of cholera toxin but at 20 degrees C and 16 degrees C a cholera toxin stimulation was still observed. These results bear strongly against the hypothesis that the glycoprotein hormones TSH and LH acetivate adenylate cyclase by a mechanism identical to cholera toxin.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004789:Enzyme Activation; D005260:Female; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D007986:Luteinizing Hormone / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*
D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D013972:Thyrotropin; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases