Multiple sites for interaction of prostaglandin and vasopressin in toad urinary bladder.
The interaction of vasopressin with prostaglandins were examined in the toad bladder by determining water flows, cAMP levels, and cAMP-dependent protein kinase activity. Both water flow and activation of cAMP-kinase in response to vasopressin were enhanced after prostaglandin inhibition, consistent with inhibition of vasopressin-induced cAMP generation by endogenous prostaglandins. On the other hand exogeneous PGE stimulated cAMP generation. PGE1 (10(-7) M) alone did not increase water flow but activated kinase more than vasopressin only. Addition of PGE1 (10(-7) M) and vasopressin inhibited water flow as compared with vasopressin along but increased the kinase ratio above that with vasopressin only. PGE2 (10(-5) M) increased the cAMP content and kinase ratio even more than vasopressin but again resulted in no water flow. Addition of vasopressin and PGE2 (10(-5) M) increased water flow but did not alter cAMP content or the kinase ratio compared with PGE2 alone. Similar results were obtained with PGE1. Accordingly, prostaglandin dissociates cAMP levels and kinase ratio from the hydroosmotic response, suggesting that PGE2 inhibits steps distal to cAMP. Consistent with this, in bladders pretreated with naproxen or meclofenamate, PGE2 (10(-8) to 10(-6) M) inhibited the response to submaximal doses of cAMP (5 mM) or 8-bromo-cAMP (0.03 mM). Furthermore, pretreatment with naproxen significantly enhanced the response to cAMP (5 mM). These studies provide evidence for vasopressin-PGE interaction at the site of cAMP generation and also at a step(s) unrelated to cAMP generation.
D000818:Animals; D002025:Bufonidae; D002463:Cell Membrane Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004848:Epithelium / Q000201:enzymology; D009288:Naproxen / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D001743:Urinary Bladder / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D011458:Prostaglandins E; D014667:Vasopressins; D009288:Naproxen; D000242:Cyclic AMP; D011494:Protein Kinases