THE RELEASE OF PARATHYROID-HORMONE AND THE EXOCYTOSIS OF A PROTEOGLYCAN ARE MODULATED BY EXTRACELLULAR CA2+ IN A SIMILAR MANNER

Secretion of parathyroid hormone (PTH) is regulated in part by a class ical ''stimulus-secretion'' pathway responsive to catecholamines. The primary physiological modulator of PTH exocytosis in parathyroid cells , however, is extracellular free Ca2+. Ca2+-modulated PTH release exhi bits several characteristics suggestive of constitutive secretion. The aim of this work was to obtain further information about the possible intracellular origins of Ca2+-modulated exocytosis in parathyroid cel ls. Freshly dissociated bovine parathyroid cells labeled with [S-35]su lfate synthesized a soluble chondroitin/dermatan sulfate proteoglycan (M(r) similar to 90-150 K) that was secreted into the medium. The expo rt of [S-35]sulfated proteoglycan satisfied several criteria that gene rally define constitutive release: 1) export is detected in the medium shortly (7-15 min) after a 5-min pulse, 2) there is minimal intracell ular storage after equilibrium labeling (because of combined processes of rapid release and intracellular degradation), and 3) there is inse nsitivity to stimulation with isoproterenol, a known secretagogue in p arathyroid cells. Nevertheless, the increase in extracellular Ca2+ fro m 0.5 to 2.0 mM reduced the export of the [S-35]sulfated proteoglycan from 60% of total labeled to 30%. ln addition, a secreted pool of immu noreactive PTH and [S-35]sulfated proteoglycan was modulated by extern al Ca2+ to the same degree and sensitivity, although isoproterenol was more effective in stimulating the release of PTH than that of proteog lycan. Together, our experimental results show that in the parathyroid cell extracellular Ca2+ modulates negatively the export of both PTH a nd proteoglycan, a putative marker for constitutive secretion. We furt her suggest that a portion of newly synthesized PTH also enters this p athway, whereas another portion proceeds to an isoproterenol-releasabl e compartment from which the proteoglycan is largely excluded.