STIMULATION OF ADENYLYL-CYCLASE MEDIATED BY PHOSPHOLIPASE C-LINKED M(3) MUSCARINIC RECEPTOR IN HUMAN NEUROBLASTOMA SK-N-BE(2)C CELLS
SCIE
SCOPUS
- Title
- STIMULATION OF ADENYLYL-CYCLASE MEDIATED BY PHOSPHOLIPASE C-LINKED M(3) MUSCARINIC RECEPTOR IN HUMAN NEUROBLASTOMA SK-N-BE(2)C CELLS
- Authors
- SUH, BC; KIM, KT
- Date Issued
- 1995-06
- Publisher
- LIPPINCOTT-RAVEN PUBL
- Abstract
- Muscarinic receptor in human neuroblastoma SK-N-BE(2)C cells was identified and characterized. Treatment of the cells with carbachol evoked the generation of inositol 1,4,5-trisphosphate (IP3) with a peak level reached at 1 min after stimulation. Carbachol increased intracellular Ca2+ ([Ca2+](i)) with an EC(50) value of 35 mu M. In addition, carbachol produced a 1.3-3-fold increase in the cyclic AMP (cAMP) level compared with untreated control and elevated synergistically the cAMP level in the treatment with prostaglandin E(2) (PGE(2)). The M(3) antagonist p-fluorohexahydrosiladifenidol (IC50 = 0.5-0.8 mu M) inhibited the increases in [Ca2+](i), IP3, and cAMP more effectively than the M(1) antagonist pirenzepine (IC50 = 5-9 mu M) and the M(2) antagonist methoctramine (IC50 = 20-30 mu M) The involvements of [Ca2+](i) elevation and protein kinase C activation induced by phospholipase C activation were tested in the carbachol-induced cAMP production. The calcium chelator BAPTA/AM (75 mu M) inhibited significantly the synergistic effects of carbachol and PGE(2) on the production of cAMP, whereas the Ca2+ ionophore ionomycin (1 mu M) clearly enhanced PGE(2)-induced cAMP production. However, phorbol 12-myristate 13-acetate did not enhance PGE(2)-stimulated cAMP production. These data suggest that phospholipase C-linked M(3) receptors are present and that stimulation of the receptors activates adenylyl cyclase, at least in part, by the Ca2+-dependent system in the neuronal cells.
- Keywords
- SK-N-BE(2)C HUMAN NEUROBLASTOMA; MUSCARINIC M(3) RECEPTORS; CA2+ MOBILIZATION; CYCLIC AMP ACCUMULATION; INOSITOL 1,4,5-TRISPHOSPHATE; PROTEIN-KINASE-C; SK-N-SH; INOSITOL 1,4,5-TRISPHOSPHATE BINDING; NEURO-BLASTOMA CELLS; BETA-GAMMA-SUBUNITS; CYCLIC-AMP; PHOSPHOINOSITIDE HYDROLYSIS; MOLECULAR-BASIS; PHORBOL ESTERS; SH-SY5Y
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/21787
- DOI
- 10.1046/j.1471-4159.1995.64062500.x
- ISSN
- 0022-3042
- Article Type
- Article
- Citation
- JOURNAL OF NEUROCHEMISTRY, vol. 64, no. 6, page. 2500 - 2508, 1995-06
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