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Parathyroid Ca(2+)-conducting currents are modulated by muscarinic receptor agonists and antagonists.

Artikel i vetenskaplig tidskrift
Författare W Chang
T H Chen
S A Pratt
B Yen
Michael Fu
D Shoback
Publicerad i The American journal of physiology
Volym 273
Nummer/häfte 5 Pt 1
Sidor E880-90
ISSN 0002-9513
Publiceringsår 1997
Publicerad vid Wallenberglaboratoriet
Sidor E880-90
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord Acetylcholine, pharmacology, Amino Acid Sequence, Animals, Atropine, pharmacology, Base Sequence, Calcium Channels, biosynthesis, drug effects, physiology, Cattle, Cells, Cultured, Cyclic AMP, metabolism, DNA Primers, Humans, Inositol Phosphates, metabolism, Kinetics, Membrane Potentials, drug effects, physiology, Molecular Sequence Data, Muscarine, pharmacology, Muscarinic Agonists, pharmacology, Muscarinic Antagonists, pharmacology, Nifedipine, pharmacology, Parathyroid Glands, drug effects, physiology, Polymerase Chain Reaction, Receptors, Muscarinic, biosynthesis, genetics, Sequence Alignment, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Tetraethylammonium, pharmacology
Ämneskategorier Fysiologi

Sammanfattning

Parathyroid cells express Ca(2+)-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 approximately equal to 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.

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