Parathyroid Ca²⁺-conducting currents are modulated by muscarinic receptor agonists and antagonists

Abstract

Parathyroid cells express Ca2+-conducting cation currents, which are activated by raising the extracellular Ca2+ concentration ([Ca2+]o) and blocked by dihydropyridines. We found that acetylcholine (ACh) inhibited these currents in a reversible, dose-dependent manner (50% inhibitory concentration ≈10−8 M). The inhibitory effects could be mimicked by the agonist (+)-muscarine. The effects of ACh were blunted by the antagonist atropine and reversed by removing ATP from the pipette solution. (+)-Muscarine enhanced the adenosine 3′,5′-cyclic monophosphate (cAMP) production by 30% but had no effect on inositol phosphate accumulation in parathyroid cells. Oligonucleotide primers, based on sequences of known muscarinic receptors (M1-M5), were used in reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify receptor cDNA from parathyroid poly (A)+ RNA. RT-PCR products displayed >90% nucleotide sequence identity to human M2- and M4-receptor cDNAs. Expression of M2-receptor protein was further confirmed by immunoblotting and immunocytochemistry. Thus parathyroid cells express muscarinic receptors of M2 and possibly M4 subtypes. These receptors may couple to dihydropyridine-sensitive, cation-selective currents through the activation of adenylate cyclase and ATP-dependent pathways in these cells.

Negative Association between Serum Parathyroid Hormone Levels and Urinary Perchlorate, Nitrate, and Thiocyanate Concentrations in U.S. Adults: The National Health and Nutrition Examination Survey 2005–2006

“…In addition to calcium and vitamin D as major regulators of PTH synthesis and secretion, other factors may affect serum PTH levels. For incidence, PTH secretion is modulated by the activity of the autonomous nervous system [22] , [23] . Recently, hyperparathyroidism has been identified as a novel feature of primary aldosteronism [24] .…”

Coupling of Calcium Receptors to Inositol Phosphate and Cyclic AMP Generation in Mammalian Cells and Xenopus laevis Oocytes and Immunodetection of Receptor Protein by Region-Specific Antipeptide Antisera

“…Membrane proteins were extracted from HEK 293 cells and newborn calf parathyroid glands (19) and electrophoresed by standard sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) using a 7.5% gel (20) . Proteins were transferred to nitrocellulose paper using a transfer buffer consisting of methanol (5%), Tris (25 mM), and glycine (192 mM) using Transblot (BioRad, Hercules, CA, U.S.A.) as specified by the manufacturer.…”

PTH Pulsatility but Not Calcium Sensitivity Is Restored after Total Parathyroidectomy with Heterotopic Autotransplantation

“…Sympathetic fibers reaching the parathyroids originate in the superior cervical ganglion, and vagal fibers from the dorsal motor nucleus project via the thyroid and inferior laryngeal nerves to intraparathyroidal cholinergic ganglia. Nerve endings extend into the endocrine cell parenchyma, where both adrenergic and cholinergic receptors are present (7,8). Whereas parasympathetic input inhibits basal and calcium-responsive PTH secretion (9), the sympathetic nervous system exerts either stimulatory and inhibitory effects via ␤-and ␣-adrenergic receptors, respectively (10).…”