Substance P regulates PTH secretion through the neurokinin-1 receptor

Area of Science:

• Neuroendocrinology
• Cellular Physiology

Background:

• Parathyroid hormone (PTH) secretion is primarily regulated by serum ionized calcium (Ca2+).
• Nerve fibers containing neuropeptides have been identified in the parathyroid gland, suggesting potential neural regulation of PTH secretion.

Purpose of the Study:

• To investigate whether the neuropeptide substance P (SP) plays a role in regulating PTH secretion.
• To elucidate the specific receptor mechanism involved in SP-mediated effects on PTH release.

Main Methods:

• Utilized dispersed porcine parathyroid cells for in vitro studies.
• Assessed the effects of SP, NK-1, NK-2, and NK-3 receptor agonists on PTH secretion under varying CaCl2 concentrations.
• Employed RT-PCR to detect NK-1 receptor mRNA expression in parathyroid cells.
• Investigated the role of a selective NK-1 receptor antagonist (LY306740) in reversing SP's effects.

Main Results:

• SP reversibly inhibited CaCl2-induced PTH secretion at low calcium concentrations (0.5 mM CaCl2) with an IC50 of 0.29 nM.
• A selective NK-1 receptor agonist mimicked SP's inhibitory effect on PTH secretion at 0.5 mM CaCl2 (IC50 = 0.21 nM).
• NK-2 and NK-3 receptor agonists showed significantly less activity compared to SP and the NK-1 agonist.
• The NK-1 antagonist LY306740 specifically reversed the effects of SP on PTH secretion.
• NK-1 receptor mRNA was detected in porcine parathyroid cells.

Conclusions:

• Substance P (SP) acts as a regulator of PTH secretion.
• This regulation occurs through the activation of NK-1 receptors located on parathyroid cells.
• A novel neuroendocrine pathway involving SP and NK-1 receptors in modulating PTH secretion has been identified.