Forskolin mimics the hydrosmotic action of vasopressin in the urinary bladder of toads Bufo marinus.
Net water flow JW was measured across the urinary bladder of toads Bufo marinus and averaged over periods of 1 min by means of a volumetric, automatic technique. The diterpene forskolin, an activator of adenylate cyclase bypassing the hormonal receptor subunit, induced a rapid, reversible, dose-dependent increase in osmotic water permeability, Pf, very similar to that induced by vasopressin. At 1.1 microM, forskolin induced a half-maximal response. At 5 microM forskolin caused a near maximal response and Pf increased from 1.66 +/- 0.15 to 66.6 +/- 2.99 microns s-1. In bladders pre-exposed to 5 microM-forskolin, further significant increases in Pf were obtained by their subsequent exposure to vasopressin, cyclic AMP, theophylline or serosal hypertonicity. The similarity of the forskolin and vasopressin actions was further demonstrated by the finding that substances causing enhancement (quercetin) or inhibition (trifluoperazine, vanadate, silver, cobalt, manganese and Ca2+-free Ringer solution) of the vasopressin response, induced parallel changes in the forskolin response. Three agents, however, induced dissimilar effects on vasopressin and forskolin: high K+ potentiated vasopressin but inhibited forskolin; methohexital and diamide inhibited vasopressin but had no effect on forskolin. The forskolin-induced hydrosmotic response can be viewed as a new criterion for ascertaining the messenger role of cycle AMP in the the hydrosmotic effect of vasopressin.
De Sousa
R C
RC
Grosso
A
A
D000818:Animals; D002024:Bufo marinus; D005576:Colforsin; D000242:Cyclic AMP / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology; D004224:Diterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008723:Methohexital / Q000494:pharmacology; D009995:Osmosis / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D001743:Urinary Bladder / Q000378:metabolism*; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014867:Water / Q000378:metabolism*
D004224:Diterpenes; D014867:Water; D003958:Diamide; D014667:Vasopressins; D005576:Colforsin; D011794:Quercetin; D013806:Theophylline; D000242:Cyclic AMP; D008723:Methohexital