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1 Endocrine Research Unit,
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.
calcium currents; calcium channel; calcium receptor; adenylate cyclase; adenosine 3',5'-cyclic monophosphate
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W. Chang, T.-H. Chen, S. Pratt, and D. Shoback Regulation of extracellular calcium-activated cation currents by cAMP in parathyroid cells Am J Physiol Endocrinol Metab, August 1, 1998; 275(2): E213 - E221. [Abstract] [Full Text] [PDF] |
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