Selective inhibition of beta(2)-adrenergic receptor-mediated cAMP generation by activation of the P2Y(2) receptor in mouse pineal gland tumor cells
SCIE
SCOPUS
- Title
- Selective inhibition of beta(2)-adrenergic receptor-mediated cAMP generation by activation of the P2Y(2) receptor in mouse pineal gland tumor cells
- Authors
- Suh, BC; Kim, JS; Namgung, U; Han, S; Kim, KT
- Date Issued
- 2001-06
- Publisher
- BLACKWELL SCIENCE LTD
- Abstract
- Rhythmic noradrenergic signaling from the hypothalamic clock in the suprachiasmatic nucleus to the pineal gland causes an increase in intracellular cAMP which regulates the circadian fluctuation of melatonin synthesis. The activation of phospholipase C (PLC)-coupled P2Y(2) receptors upon treatment with ATP and UTP exclusively inhibited the isoproterenol-stimulated cAMP production in mouse;pineal gland tumor cells. However, the activation of other PLC-coupled receptors including P2Y(1) and bombesin receptors had little or no effect on the isoproterenol-stimulated cAMP production. Also, ATP did not inhibit cAMP production caused by forskolin, prostaglandin Eg, or the adenosine analog NECA. These results suggest a selective coupling between signalings of P2Y2 and pp-adrenergic receptors. The binding of [H-3]CGP12177 to PP. adrenergic receptors was not effected by the presence of ATP or UTP. lonomycin decreased the isoproterenol-stimulated cAMP production, whereas phorbol 12-myristate 13-acetate slightly potentiated the isoproterenol response. Chelation of intracellular Ca2+, however, had little effect on the ATP-induced inhibition of cAMP production, while it completely reversed the ionomycin-induced inhibition. Treatment of cells with pertussis toxin almost completely blocked the inhibitory effect of nucleotides. Pertussis toxin also inhibited the nucleotide-induced increase in intracellular Ca2+ and inositol 1,4,5-trisphosphate production by 30-40%, suggesting that the ATP-mediated inhibition of the cAMP generation and the partial activation of PLC are mediated by pertussis toxin-sensitive Gi-protein. We conclude that one of the functions of P2Y2 receptors on the pineal gland is the selective inhibition of P-adrenergic receptor-mediated signaling pathways via the inhibitory G-proteins.
- Keywords
- beta(2)-adrenergic receptor; cAMP generation; extracellular ATP; P2Y(2) receptor; PGT-beta mouse pineal gland tumor cells; PROTEIN-KINASE-C; RAT PINEALOCYTES; PHOSPHOLIPASE-C; P2-PURINERGIC RECEPTORS; N-ACETYLTRANSFERASE; CIRCADIAN-RHYTHMS; ADENYLYL-CYCLASE; CYTOSOLIC CA2+; MELATONIN; IDENTIFICATION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/19506
- DOI
- 10.1046/j.1471-4159.2001.00367.x
- ISSN
- 0022-3042
- Article Type
- Article
- Citation
- JOURNAL OF NEUROCHEMISTRY, vol. 77, no. 6, page. 1475 - 1485, 2001-06
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