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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

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

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