Substance P regulates PTH secretion through the neurokinin-1 receptor.
The primary regulator of PTH secretion is serum ionized Ca(2+); however, neuropeptide-containing nerve fibers have been localized to the parathyroid gland. The purpose of this study was to determine whether or not substance P (SP) regulates PTH secretion. In dispersed porcine parathyroid cells, SP reversibly inhibited 0.5 mM CaCl(2)-induced PTH secretion (IC(50) = 0.29 nM) and had no effect at CaCl(2) concentrations of 1.5 mM and greater. At 0.5 mM CaCl(2), treatment with a NK-1 selective receptor agonist resulted in a concentration-dependent decrease in PTH secretion (IC(50) = 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 enantiospecific reversal of the effects of SP on PTH secretion was observed with LY306740, a potent selective NK-1 receptor antagonist (K(i) = 0.125 nM). In porcine parathyroid cells, expression of mRNA for the NK-1 receptor was observed using RT-PCR. In summary, a novel neuroendocrine pathway is described whereby the neuropeptide, SP, regulates PTH secretion through NK-1 receptors.
Galvin
R J
RJ
Endocrine Division, Neurosciences Division, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. Galvin_Rachelle_J_S@Lilly.com
Babbey
L E
LE
Hipskind
P A
PA
Lamar
T
T
George
C A
CA
Baez
M
M
Gitter
B D
BD
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D064729:Neurokinin-1 Receptor Antagonists; D010280:Parathyroid Glands / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000819:agonists; D018042:Receptors, Neurokinin-3 / Q000819:agonists; D013373:Substance P / Q000494:pharmacology*; D013552:Swine
D000081:Acetamides; C102280:LY 306740; D064729:Neurokinin-1 Receptor Antagonists; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D013373:Substance P