Substance P regulates PTH secretion through the neurokinin-1 receptor

The primary regulator of PTH secretion is serum ionized Ca2+; however, neur opeptide-containing nerve fibers have been localized to the parathyroid gla nd. The purpose of this study was to determine whether or not substance P ( SP) regulates PTH secretion. In dispersed porcine parathyroid cells, SP rev ersibly inhibited 0.5 mM CaCl2-induced PTH secretion (IC50 = 0.29 nM) and h ad no effect at CaCl2 concentrations of 1.5 mM and greater. At 0.5 mM CaCl2 , treatment with a NK-1 selective receptor agonist resulted in a concentrat ion-dependent decrease in PTH secretion (IC50 = 0.21 nM). In contrast, NK-2 and NK-3 receptor agonists were approximately 100-fold less active than SP or the NK-1 receptor selective agonist. An enantio-specific reversal of th e effects of SP on PTH secretion was observed with LY306740, a potent selec tive NK-1 receptor antagonist (K-i = 0.125 nM). In porcine parathyroid cell s, expression of mRNA for the NK-1 receptor was observed using RT-PCR. In s ummary, a novel neuroendocrine pathway is described whereby the neuropeptid e, SP, regulates PTH secretion through NK-1 receptors. (C) 2000 Academic Pr ess.