Anti-calmodulin agents affect osmotic and angiotensin II-induced vasopressin release.
Calcium ions and particularly calcium influx play a crucial part in initiating the intracellular events that result in arginine vasopressin (AVP) release to both osmotic and nonosmotic stimuli. Calmodulin appears to modulate the effects of calcium on synaptic transmission and hormone release in other systems. This study tested the effects of three distinct classes of anti-calmodulin agents on the release of AVP to either a rise in osmolality of 20 mosmol/kg water or to 1 X 10(-5) angiotensin II (ANG II) in cultured hypothalamo-neurohypophysical complexes. Micromolar concentrations of R 24571, the active naphthalenesulfonamides, W 7 and W 13, and trifluoperazine (TFP) inhibited AVP release to osmotic stimulation. In contrast, W 5, a severalfold less active anti-calmodulin agent, had no effect on osmotically stimulated AVP release. The active naphthalenesulfonamides, but not R 24571 or TFP, blocked release of AVP to ANG II. In contrast, neither R 24571 nor TFP inhibited AVP release to ANG II stimulation. Collectively, the data demonstrated a dissociation between inhibition of AVP release and the anti-calmodulin properties of the drugs, thereby suggesting that nonspecific actions masked the calmodulin-blocking effects of the drugs or that the inhibition occurred by some alternative mechanism(s).
Rossi
N F
NF
Department of Medicine, Wayne State University, School of Medicine, Detroit, Michigan 48201.
Schrier
R W
RW
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D046508:Culture Techniques; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D007093:Imidazoles; D013449:Sulfonamides; D000804:Angiotensin II; D001127:Arginine Vasopressin; D014268:Trifluoperazine; C031938:calmidazolium; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide