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Influence of age on control of norepinephrine release: Ca2+ channels and dopamine D2 receptors
1Department of Pharmacology, College of Medicine, University of California, Irvine 92717.
Abstract:
Possible age-related changes in the roles of L- and N-type Ca2+ channels and dopamine D2 receptors in control of norepinephrine release were investigated in tail arteries of F-344 rats. Nifedipine had no effect on stimulation-evoked tritium efflux at 6 or 24 months of age; however, omega-conotoxin GVIA reduced efflux by 70 to 80% at both ages even when frequency of stimulation was altered. Activation of prejunctional dopamine D2 receptors by the selective agonist N-0923 [(S)-(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin++ +] inhibited contractile responses to transmural nerve stimulation in a frequency and concentration-dependent manner. Effects were similar from 6 to 26 months. Furthermore inhibition by N-0923 of stimulation-evoked [3H]norepinephrine efflux was not different at 12 and 24 months. Thus, N-type Ca2+ channels predominate in control of norepinephrine release, and this is unchanged with advancing age or stimulation intensity. Furthermore, D2 receptor-mediated inhibition of norepinephrine release is not altered with advancing age.