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Mechanisms of Cytosolic Ca 2+ Suppression By Prostaglandin E 2 Receptors in Rat Melanotrophs
Author(s) -
Nagata T.,
Harayama N.,
Sasaki N.,
Inoue M.,
Tanaka K.,
Toyohira Y.,
Uezono Y.,
Maruyama T.,
Yanagihara N.,
Ueta Y.,
Shibuya I.
Publication year - 2003
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.2003.00864.x
Subject(s) - prostaglandin e2 receptor , receptor , medicine , endocrinology , agonist , chemistry , extracellular , prostaglandin e2 , dopamine , biology , biochemistry
We have previously reported that voltage‐dependent Ca 2+ (VDC) channels of rat melanotrophs are inhibited by prostaglandin E 2 (PGE 2 ). In this study, mechanisms involved in the inhibitory actions of PGE 2 receptors of rat melanotrophs were analysed using reverse transcriptase‐polymerase chain reaction (RT‐PCR), Ca 2+ ‐imaging and whole‐cell, patch‐clamp techniques with recently developed EP agonists, each of which is selective for the known four subclasses of EP receptors (EP 1–4 ). PGE 2 reversibly suppressed the cytosolic Ca 2+ concentration ([Ca 2+ ] i ). The maximum reduction in [Ca 2+ ] i by PGE 2 was comparable to that by dopamine or to that by extracellular Ca 2+ removal. RT‐PCR analysis of all four EP receptors revealed that EP 3 and EP 4 receptor mRNAs were expressed in the intermediate lobe. The effects of PGE 2 to suppress [Ca 2+ ] i were mimicked by the selective EP 3 agonist, ONO‐AE‐248, whereas three other EP agonists, ONO‐DI‐004 (EP 1 ), ONO‐AE1‐259 (EP 2 ) and ONO‐AE1‐329 (EP 4 ), had little or no effect on [Ca 2+ ] i . All four G‐protein activated inward rectifying K + (GIRK) channel mRNAs were identified in intermediate lobe tissues by RT‐PCR. Dopamine concentration‐dependently activated GIRK currents, whereas PGE 2 did not activate GIRK currents, even at the concentration causing maximal inhibition of VDC channels. These results suggest that PGE 2 acts on EP 3 receptors to suppress Ca 2+ entry of rat melanotrophs by selectively inhibiting VDC channels of these cells. We have compared the possible cellular and molecular mechanisms of inhibition by dopamine and PGE 2 .