Prostaglandin E2Stimulation of Adenosine 3′,5′-Monophosphate Accumulation and Parathyroid Hormone Release in Dispersed Bovine Parathyroid Cells*

Abstract

Recent studies suggest that several secretagogues, in addition to Ca, may be important in the regulation of parathyroid hormone (PTH) secretion. Employing a dispersed bovine parathyroid cell system developed in this laboratory, we investigated the effects of prostaglandin E2 (PGE2) on the generation of c[cyclic]AMP and subsequent PTH release. PGE2 (10-5 M) increased total cAMP (cells and medium) approximately 1.5 to 2.5-fold over the control at 15 min. This effect was not altered by (-) propranolol (10-6 M), .alpha.-flupenthixol (10-5 M) or phentolamine (10-5 M). Intracellular cAMP rose to peak concentration approximately 5 min after the addition of PGE2 and extracellular cAMP increased linearly with time. Half-maximal stimulation for intracellular cAMP as well as total cAMP was observed with .apprx. 10-6 M PGE2. PTH release rose 75% over control at 15 min after addition of PGE2 and was half-maximally stimulated by .apprx. 3 .times. 10-7 M PGE2. PGE2-mediated release was greatest at low Ca concentration (0.5 mM) and was suppressed by a Ca concentration of 2.0 mM. Naproxen (10-4 M), a potent cyclooxygenase inhibitor, did not alter the increase in PTH release after exposure to low extracellular Ca. These results support the possibility that intracellular cAMP is linked to PTH release and suggest a possible role for prostaglandins in the regulation of PTH secretion.