<i>In Vitro</i>Studies of the Adenosine 3′,5′-Monophosphate (cAMP) Response of Embryonic Rat Calvaria to Bovine Parathyroid Hormone-(l–84) [bPTH-(l–84)], bPTH-(l–34), and bPTH-(3–34) and the Loss of cAMP Responsiveness after Prolonged Incubation

Abstract

The time course of the stimulation of cAMP levels in embryonic rat calvaria by bovine parathyroid hormone- (1–84) [bPTH-(l–84)], bPTH-(l–34), and [Nle-8, Nle-18, Tyr-34]bPTH-(l–34) amide was studied at concentrations of 8 × 10−8M. After addition of the hormone preparations, cAMP levels reached a maximum at 10 min and declined nearly to basal levels by 4 h. Incubation of rat calvaria for 2 h on a solid coagulum with the same concentration (8 × 10−8M) of bPTH- (1–84) resulted in an almost complete loss of responsiveness (no significant further rise of the cAMP level) upon renewed addition of the hormone. After preincubation of the calvaria with bPTH- (1–34) or [Nle-8, Nle-18, Tyr-34]bPTH-(l–34) amide, some responsiveness remained, though at a level significantly less than that seen with calvaria preincubated in a standard medium. No effect on responsiveness to bPTH-(l–84) was found after preincubation of the calvaria with bPTH-(3–34) (8 × 10−8M), [Nle-8, Nle-18, Tyr-34]bPTH-(3–34) amide (8 × 10−8M), or bPTH-(53–84) (1 × 10−6M). After prolonged incubation of embryonic rat calvaria with bPTH-(l–84), the loss of responsiveness to bPTH-(l–84) was time and concentration dependent; the responsiveness was restored after incubation for 24 h in a standard medium. Treatment of calvaria for 2 h with epinephrine (1.7 × 10−5M) or prostaglandin E, (2.5 × 10−6M) also caused desensitization to bPTH-(l–84). From these findings it is concluded that in embryonic rat calvaria, a heterologous desensitization occurs as well. However, no desensitization was observed after preincubation of calvaria with 1,25-dihydroxyvitamin D.i (1 × 10−7M) or calcitonin (1.2 × 10−8M). (Endocrinology106: 2013, 1980)