Evidence that monensin inhibits vasopressin-stimulated water flow at an early step in the receptor-adenylate cyclase sequence.
Monensin, a highly selective sodium ionophore, inhibits vasopressin-stimulated water flow in toad urinary bladder pretreated with naproxen, an inhibitor of prostaglandin synthesis. Inhibition is partially dependent on the presence of sodium in the serosal medium, but not on serosal calcium. We have found that monensin does not inhibit water flow generated by forskolin, cyclic AMP, or isobutyl methyl xanthine (MIX); indeed, an enhancement of water flow was seen following cAMP and MIX, as well as following 0.2 microM forskolin. Our findings suggest that monensin uncouples the vasopressin-receptor-G protein-adenylate cyclase sequence at some early step, by a mechanism that remains unknown, but that may directly or indirectly involve intracellular sodium.
Franki
N
N
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Mosenkis
B
B
Hays
R M
RM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001834:Body Water / Q000502:physiology; D002024:Bufo marinus; D005576:Colforsin / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008985:Monensin / Q000494:pharmacology*; D009288:Naproxen / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000502:physiology*; D017483:Receptors, Vasopressin; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009288:Naproxen; D008985:Monensin; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine