Inhibition of vasopressin-sensitive cAMP accumulation by alpha 2-adrenoceptor agonists in collecting tubules is species dependent.
The ability of alpha 2-adrenoceptor agonists to inhibit vasopressin (VP)-stimulated cAMP accumulation in collecting tubules and to inhibit the antidiuretic effect of VP in rats is clearly established. However, in other species, such as the dog, alpha 2-adrenoceptor-induced inhibition of VP action has not been convincingly demonstrated. In the present study, we examined the effects of epinephrine and other alpha 2-adrenoceptor agonists on VP-stimulated cAMP accumulation in inner medullary collecting tubule cells and/or cortical collecting tubules from a number of species. Epinephrine, oxymetazoline, clonidine, and guanabenz inhibited VP-induced cAMP formation in rat inner medullary collecting tubule cells with IC50s ranging from 10 to 30 nM. However, epinephrine or guanabenz had no effect on VP-stimulated cAMP formation in cells from dog, pig, rhesus monkey, or human inner medulla. Similarly, epinephrine inhibited VP-induced cAMP accumulation in cortical collecting tubules dissected from rat kidneys but not from dog or rabbit kidneys. We conclude that there is a marked species difference in the ability of alpha 2-adrenoceptor agonists to inhibit VP-induced cAMP formation at the tubular level. This may explain the difficulty in demonstrating an alpha 2-adrenoceptor agonist-induced inhibition of VP action in other species such as dog and man.
Edwards
R M
RM
Department of Pharmacology, SmithKline Beecham, Pharmaceuticals, King of Prussia, Pa. 19406-0939.
Stack
E J
EJ
Gellai
M
M
Brooks
D P
DP
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002648:Child; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004285:Dogs; D005260:Female; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000201:enzymology; D007687:Kidney Tubules, Proximal / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature; D014667:Vasopressins / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D010281:Parathyroid Hormone; D014667:Vasopressins; D000242:Cyclic AMP