ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: In this study the subunits of the dihydropyridine-sensitive L-type Ca2+ 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 α1D, α2b, β2, and β4 Ca2+-channel subunit mRNAs. Other α1 subunit transcripts were either not expressed or present at very low levels, indicating that the pinealocytes express predominantly α1D 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 α1D 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1997.68031078.x
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