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Calcium stimulates luteinizing-hormone (lutropin) exocytosis by a mechanism independent of protein kinase C.

Abstract:
Using permeabilized gonadotropes, we examined whether Ca2(+)-stimulated luteinizing-hormone (LH) exocytosis is mediated by the Ca2(+)-activated phospholipid-dependent protein kinase (protein kinase C). In the presence of high [Ca2+]free (pCa 5), alpha-toxin-permeabilized sheep gonadotropes secrete a burst of LH and then become refractory to maintained high [Ca2+]free. The protein kinase C activator phorbol myristate acetate (PMA) is able to stimulate further LH release from cells made refractory to high [Ca2+]free, suggesting that Ca2+ does not stimulate LH release by activating protein kinase C. Staurosporine, a protein kinase C inhibitor, inhibited PMA-stimulated (50% inhibition at 20 nM), but not Ca2(+)-stimulated, LH exocytosis. In cells desensitized to PMA by prolonged exposure to a high PMA concentration, Ca2(+)-stimulated LH exocytosis (when corrected for depletion of total cellular LH) was not inhibited. Ba2+ was able to stimulate LH exocytosis to a maximal extent similar to Ca2+, although higher Ba2+ concentrations were necessary. Ba2+ and Ca2+ stimulated LH exocytosis with a similar time course, and both were inhibitory at high concentrations. Furthermore, cells made refractory to Ca2+ were also refractory to Ba2+. These data strongly suggest that Ba2+ and Ca2+ act through the same mechanism. Since Ba2+ is a poor activator of protein kinase C, these findings are additional evidence against a major role for protein kinase C in mediating Ca2(+)-stimulated LH exocytosis.

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Institution:
University of Oxford
Division:
MSD
Department:
Pathology Dunn School
Role:
Author


Journal:
Biochemical journal More from this journal
Volume:
268
Issue:
2
Pages:
493-498
Publication date:
1990-06-01
EISSN:
1470-8728
ISSN:
0264-6021


Language:
English
Keywords:
Pubs id:
pubs:13365
UUID:
uuid:188955af-5452-4bf5-a05e-0469b7b0619e
Local pid:
pubs:13365
Source identifiers:
13365
Deposit date:
2012-12-19
ARK identifier:

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