Thyroid parafollicular cells are neural crest-derived endocrine cells which produce calcitonin and serotonin. The secretory vesicles of parafollicular cells acidify when secretion is induced by increased extracellular Ca2+ or TSH. Scientists have 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 C cells 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. So, it has been concluded that acidification of C cells 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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