Correlation between cAMP in isolated frog skin epithelium and stimulation of sodium transport and osmotic water flow by antidiuretic hormone and phosphodiesterase inhibitors.
The cAMP level in isolated frog skin epithelia was stimulated by a range of concentrations of the antidiuretic hormone arginine vasotocin (AVT) and compared to active sodium transport measured as short-circuit current (SCC). The response of SCC and osmotic water flow (OWF) to AVT was investigated in a separate series. SCC was approximately three times more sensitive to AVT than OWF. Measurable increments of cAMP above the basal level were found only with AVT concentrations eliciting half-maximal response or more of SCC. Two models are offered to explain the findings: (A) Total SCC depends on epithelial cAMP with a sigmoidal relationship. (B) Epithelial cAMP exists in two separate pools of which only one is accessible to AVT, and SCC stimulation depends on cAMP in the AVT-controlled pool in a simple saturable fashion. Correlation between cAMP and SCC after stimulation with theophylline resembled that after AVT. Papaverine (10 microM) induced only small changes in SCC inspite of a substantial increase in cAMP level. Higher concentrations of papaverine inhibited both basal and AVT-stimulated SCC, while the cAMP level was further increased. This effect of papaverine may be due to a simultaneous block of another rate-determining process. Papaverine had no effect on basal or AVT-stimulated OWF despite a marked stimulation of the cAMP level. Thus, the role of cAMP as mediator of the hydroosmotic action of AVT must be questioned.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001834:Body Water / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004176:Dipyridamole / Q000494:pharmacology; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D010208:Papaverine / Q000494:pharmacology; D011893:Rana esculenta; D011896:Rana temporaria; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology; D014668:Vasotocin / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D003994:Bucladesine; D004176:Dipyridamole; D012964:Sodium; D013806:Theophylline; D010208:Papaverine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D014668:Vasotocin