Effects of the calcium channel activator BAY-K-8644 on in vitro secretion of calcitonin and parathyroid hormone.
The recently discovered calcium (Ca) channel activator BAY-K-8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate], an analog of the calcium channel blockers nifedipine and nitrendipine, was tested to determine its potential for altering hormone secretion in an in vitro system designed to study concurrent secretion of calcitonin (CT) and PTH. Addition of BAY-K-8644 (10(-4)-10(-5) M) to medium (1 mM Ca) bathing baby rat thyroparathyroids enhanced secretion of CT at least 2- to 4-fold and suppressed PTH release by as much as 75-85%. Addition of BAY-K-8644 alone to medium containing high (2.5 mM) Ca did not further enhance the already high rate of CT release, nor did it cause any further suppression of PTH secretion. BAY-K-8644 did not stimulate CT release or suppress PTH release in the absence of medium Ca. Addition of the Ca channel blocker nitrendipine (10(-5) M) inhibited CT release at either 1 or 2.5 mM Ca, and at 1 mM Ca, nitrendipine negated the simulatory effect of 10(-5) M BAY-K-8644 on CT release. However, at 2.5 mM Ca, 10(-5) M BAY-K-8644 reversed the marked inhibitory effect of 10(-5) M nitrendipine on CT release. At 1 mM Ca, PTH secretion was inhibited equally well by BAY-K-8644 and nitrendipine, and both agents together caused a further suppression of PTH release. The results indicate that Ca entry into the thyroid C-cell and parathyroid chief cell may occur via classical voltage-sensitive Ca channels and that the newly described Ca channel activator BAY-K-8644 should prove useful as a probe for studying hormone secretion in Ca-dependent secretory systems.
Cooper
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CW
Borosky
S A
SA
Farrell
P E
PE
Steinsland
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OS
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*
D010281:Parathyroid Hormone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002116:Calcitonin; D009568:Nitrendipine; D009543:Nifedipine; D002118:Calcium