Endocrinology, Vol 135, 2045-2057, Copyright © 1994 by Endocrine Society

ARTICLES

Secretogogue-induced gating of chloride channels in the secretory vesicles of parafollicular cells

H Tamir, I Piscopo, KP Liu, SC Hsiung, M Adlersberg, M Nicolaides, Q al-Awqati, EA Nunez and MD Gershon
Division of Neuroscience, New York State Psychiatric Institute, New York 10032.

Thyroid parafollicular (PF) cells are neural crest-derived endocrine cells that secrete serotonin and calcitonin. The secretory vesicles of PF cells acidify when secretion is induced by increased extracellular Ca2+ or TSH. We tested the hypothesis that acidification is regulated by secretogogue-gated Cl- channels in vesicular membranes. Cl- channel (p64) immunoreactivity was enriched in purified PF vesicles. X-Ray microanalysis showed a change in chlorine level in PF vesicles in response to secretogogue-stimulation of isolated cells. Secretogogue stimulation also altered the degree of p64 channel phosphorylation. Protein kinase and phosphatase inhibitors antagonized secretogogue- induced vesicle acidification and secretion; however, secretion could occur even when acidification was blocked. We conclude that acidification of PF vesicles is regulated by a gatable Cl- channel in vesicle membranes and that protein phosphorylation and dephosphorylation are involved in channel activation. Acidification of vesicles is not required for exocytosis.

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