Effect of anti-calmodulin agents on vasopressin release in vitro to depolarization and calcium ionophore.
Calmodulin has been implicated in transducing the effects of Ca2+ on synaptic transmission and hormone release, including osmotically-stimulated vasopressin (AVP) release. If the anti-calmodulin agents block AVP release secondary to inhibition of Ca2(+)-calmodulin interactions, these drugs should inhibit AVP release to stimuli increasing Ca2+ influx via different mechanisms. Hypothalamo-neurohypophysial complexes (HNC) were exposed to ionomycin, Bay K 8644, or veratridine either alone, with any one of three distinct chemical classes of anti-calmodulin agent, or with a Ca2+ channel antagonist. All the anti-calmodulin agents impaired AVP release to ionomycin, while Ca2+ channel blockade did not. Conversely, Ca2+ channel antagonism completely blocked AVP release in response to Bay K 8644, but the anti-calmodulin agents had no effect. None of the inhibitors prevented veratridine-induced AVP release. These results are consistent with the hypothesis that the anti-calmodulin agents tested inhibit AVP release by their membrane stabilizing properties rather than by antagonizing Ca2(+)-calmodulin in HNC. Depolarization initiated by Na+ influx may stimulate Na(+)-Ca2+ exchange by a mechanism independent of slow Ca2+ channels as well.
Rossi
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Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D014667:Vasopressins; D015759:Ionomycin; D014701:Veratridine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007770:L-Lactate Dehydrogenase; D002118:Calcium