title: Correlation between cAMP in isolated frog skin epithelium and stimulation of sodium transport and osmotic water flow by antidiuretic hormone and phosphodiesterase inhibitors.
abstract: 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.
mesh_terms: 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*
chemical_list: D003994:Bucladesine; D004176:Dipyridamole; D012964:Sodium; D013806:Theophylline; D010208:Papaverine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D014668:Vasotocin