Altered pineal adrenergic-stimulated cyclic nucleotide responses in spontaneously hypertensive rats
Chik, C.L.; Ho, A.K.
American Journal of Physiology 264(1 Pt 2): H157-H162
1993
ISSN/ISBN: 0002-9513 PMID: 8381609 Document Number: 420060
In this study, we examined the pineal adrenergic-stimulated cyclic nucleotide responses in spontaneously hypertensive rats (SHR) and their genetic control, Wistar-Kyoto rats (WKY). Treatment with norepinephrine stimulated cAMP and cGMP contents up to 50- and 12-fold in WKY pinealocytes, compared with a 35- and 4-fold increase in SHR. By contrast, there was no difference in the isoproterenol-stimulated cAMP and cGMP contents, suggesting a reduced alpha-1-adrenergic potentiation of beta-adrenergic-stimulated cGMP response in SHR pinealocytes. The altered potentiation mechanism was examined using agents that activate protein kinase C or elevate intracellular Ca-2+. In the presence of a protein kinase C activator, the isoproterenol-stimulated cAMP response was potentiated to a similar degree in WKY and SHR pinealocytes. In contrast, the potentiating effects of ionomycin and KCl on the isoproterenol-stimulated cAMP and cGMP responses in SHR pinealocytes were markedly reduced. These results indicate that in the SHR pineal gland, an altered intracellular Ca-2+-mediated event may account for the reduction in alpha-1-adrenergic potentiation of beta-adrenergic-stimulated cyclic neucleotide responses.