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α 1D L‐Type Ca 2+ ‐Channel Currents: Inhibition by a β‐Adrenergic Agonist and Pituitary Adenylate Cyclase‐Activating Polypeptide (PACAP) in Rat Pinealocytes
Author(s) -
Chik Constance L.,
Liu QinYue,
Li Bing,
Klein David C.,
Zylka Mark,
Kim Dong Sun,
Chin Hemin,
Karpinski Edward,
Ho Anthony K.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68031078.x
Subject(s) - pinealocyte , agonist , endocrinology , medicine , adenylate kinase , adenosine , pituitary adenylate cyclase activating peptide , biology , adrenergic receptor , chemistry , receptor , pineal gland , neuropeptide , vasoactive intestinal peptide , melatonin
In this study the subunits of the dihydropyridine‐sensitive L‐type Ca 2+ channels (L‐channels) expressed in rat pinealocytes were characterized using reverse transcription (RT)‐PCR analysis, and the modulation of these channels by adrenergic agonists and by pituitary adenylate cyclase‐activating polypeptide (PACAP) was studied using the patch‐clamp technique. RT‐PCR analysis showed that rat pinealocytes expressed α 1D , α 2b , β 2 , and β 4 Ca 2+ ‐channel subunit mRNAs. Other α 1 subunit transcripts were either not expressed or present at very low levels, indicating that the pinealocytes express predominantly α 1D L‐channels. Electrophysiological studies confirmed that the pineal expressed a single population of L‐channels. The L‐channel currents were inhibited by two agonists that elevate cyclic AMP: the β‐adrenergic agonist isoproterenol and PACAP. Similar inhibition was observed with a cyclic AMP analogue, 8‐bromo‐cyclic AMP. The presence of a cyclic AMP antagonist, Rp ‐adenosine 3′,5′‐cyclic monophosphorothioate, blocked the inhibition by isoproterenol and PACAP. Norepinephrine, a mixed α‐ and β‐adrenergic agonist, also inhibited the L‐channel currents, but the inhibition was smaller. The smaller inhibition by norepinephrine was secondary to the simultaneous activation of α‐ and β‐adrenergic receptors. These results indicate that (a) pinealocytes express predominantly α 1D L‐channels, and (b) the β‐adrenergic agonist isoproterenol and PACAP inhibit the L‐channel currents through elevation of cyclic AMP. However, an α‐adrenergic‐mediated mechanism also appears to be involved in the effect of norepinephrine on the L‐channel currents.