Dopamine-beta-hydroxylase: a modulator of beta adrenergic receptor activity.
The demonstrated proportionality between norepinephrine and dopamine-beta-hydroxylase released exocytotically from sympathetic nerve endings led us to explore the possible physiologic significance attached to this proportionality. The beta adrenoreceptor mediated desensitization of the hyperpolarization response to norepinephrine observed in pinealocyte membranes was rapidly reversed following the infusion of dopamine-beta-hydroxylase (DBH). This infusion also resulted in an augmented cyclic 3',5'-adenosine monophosphate (cAMP) response to isoproterenol in vitro. We suggest that the dissociation of the concentrations of norepinephrine and dopamine-beta-hydroxylase released into the synaptic cleft as a result of continuous sympathetic nerve stimulation produces a relative dopamine-beta-hydroxylase deficiency which is associated with the beta receptor desensitization. The observation that DBH restored the membrane sensitivity to NE in vitro in rat pineals, suggests that it either augments the rate at which agonist recognizes the beta receptor and couples to adenylate cyclase, or directly increases the activity of adenylate cyclase itself. The increase in cAMP generated in the presence of DBH supports such a hypothesis.
D000313:Adrenal Medulla / Q000201:enzymology; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000502:physiology; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D004299:Dopamine beta-Hydroxylase; D007545:Isoproterenol; D009638:Norepinephrine