Inhibition of the hydro-osmotic response to vasopressin and hypertonicity by phenothiazines and W7, calmodulin antagonists.
Phenothiazines and W7, calmodulin antagonists, inhibit the water flow response produced by ADH, exogenous cyclic AMP, phosphodiesterase inhibition and serosal hypertonicity. Calmodulin antagonists had no effect on osmotic water movement in the absence of hormone. Calmodulin was isolated and localized by immunofluorescence in bladder epithelial cells. Phenothiazines inhibited toad bladder calmodulin activation of phosphodiesterase and prevented fluorescent antibody recognition. The results suggest that the calcium-calmodulin process plays a role in the hydro-osmotic response to ADH and that produced by serosal hypertonicity. The calmodulin common site occurs subsequent to cyclic AMP formation, perhaps on the microtubule-microfilament system.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002024:Bufo marinus; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004848:Epithelium / Q000502:physiology; D005476:Fluphenazine / Q000494:pharmacology; D009994:Osmolar Concentration; D009995:Osmosis / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010640:Phenothiazines / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology; D001743:Urinary Bladder / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology*
D002147:Calmodulin; D010640:Phenothiazines; D013449:Sulfonamides; D014667:Vasopressins; D014268:Trifluoperazine; C017967:W 7; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D005476:Fluphenazine; D002746:Chlorpromazine