PARATHYROID-HORMONE STIMULATES CALCIUM INFLUX AND THE CAMP MESSENGER SYSTEM IN RAT ENTEROCYTES

Direct effects of parathyroid hormone (PTH) on calcium uptake by isola ted rat duodenal cell preparations enriched in enterocytes were invest igated. PTH significantly stimulated enterocyte Ca-45(2+) influx in a time-dependent (1-10 min) manner and at all doses tested (2 x 10(-13) to, 10(-7) M). The Ca2+ channel antagonists verapamil (10 mu M) and ni trendipine (1 mu M) completely blocked the stimulation of Ca2+ influx by the hormone (10(-8) M). PTH markedly increased cAMP levels in rat d uodenal cells (88, 167, and 67%, after 1, 2, and 3 min, respectively). In agreement with these observations, forskolin (adenylate cyclase ac tivator), dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), and Sp-cAMPS (cAMP analogs) mimicked, whereas Rp-cAMPS (cAMP antagonist) suppressed PTH and DBcAMP activation of enterocyte calcium uptake. Fur thermore, the effects of DBcAMP were abolished by nitrendipine. These results show direct rapid effects of PTH on duodenal cells' Ca2+ influ x, which involve the activation of a dihydropyridine-sensitive Ca2+ in flux pathway and the cAMP second messenger system.