Parathyroid hormone raises cytosolic calcium in pancreatic islets: study on mechanisms.
The pancreatic islets of Langerhans are targets for PTH and the action of the hormone on the islet is most likely mediated through the ability of PTH to increase cytosolic calcium ([Ca2+]i) of the islet cells. Although direct evidence for such an effect has been clearly demonstrated, the mechanisms through which the hormone exerts such an action are not elucidated. The present study examined these questions using pancreatic islets isolated from normal rats. Both 1-34 and 1-84 PTH produced a dose dependent increase in [Ca2+]i of the islets but the effect of the latter was significantly (P < 0.01) greater than that of the former. This action of PTH was significantly (P < 0.01) decreased by the use of PTH antagonist or by verapamil. The G protein activator (GTP gamma S) mimicked the effect of PTH while pertussis toxin and the G protein inhibitor (GDP beta S) significantly reduced the PTH-induced rise in [Ca2+]i. Dibutyryl cAMP, and phorbol ester 12-myristate 13 acetate increased [Ca2+]i of pancreatic islets in a dose dependent manner and the effect was inhibited (P < 0.01) by verapamil. Staurosporine inhibited the effect of TPA as well as of 1-84 PTH on [Ca2+]i of the islets. These data indicate that: (1) PTH increases [Ca2+]i of pancreatic islets, (2) this action is partly receptor mediated and is produced by activation of L-type calcium channels through stimulation of G protein(s), and (3) the rise in [Ca2+]i is due to both stimulation of cAMP generation and activation of protein kinase C.
Department of Medicine, University of Southern California, School of Medicine, Los Angeles.
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Fadda
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Thanakitcharu
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Smogorzewski
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Massry
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine; D019379:Teriparatide; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000470:Alkaloids; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D003994:Bucladesine; C038040:parathyroid hormone (7-34)amide, Tyr(34)-; D014700:Verapamil; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium