title: Excitation of rostral medullary pacemaker neurons with putative sympathoexcitatory function by cyclic AMP and beta-adrenoceptor agonists 'in vitro'.
abstract: This study explores the mechanism of action of catecholamines on rostral medullary pacemaker neurons with putative sympathoexcitatory function, in tissue slices. The firing rate of the pacemaker neurons of nucleus reticularis rostroventrolateralis (RVL pacemakers) was reversibly increased by agents which elevate intracellular levels of cAMP (forskolin and 8-br-cAMP). Forskolin dideoxy, an analog without action on adenylate cyclase, was ineffective and adenosine, a potential degradation product of 8-br cAMP produced inhibition exclusively and only in high doses (0.1-1 mM). The firing rate of these cells was uniformly increased by epinephrine and isoproterenol (10 microM) but unaffected by both phenylephrine (100 microM) and clonidine (up to 1 microM). These effects were abolished by pretreatment with the beta-adrenoceptor antagonist propranolol (10 microM) but they were unaffected by the alpha-antagonist phentolamine (100 microM). The indirectly-acting sympathomimetic amine tyramine (0.1-1 mM) activated all the cells tested. The effect of tyramine was antagonized by the beta-blocker pindolol and was absent 7 days after microinjection of the neurotoxin 6-hydroxydopamine into the lateral aspect of the RVL. Intracellular recordings indicated that both isoproterenol and tyramine enhanced the rate of depolarization of the pacemaker neurons during the interspike interval and produced a decrease in input resistance. After tetrodotoxin (TTX) pretreatment, isoproterenol produced a depolarization also associated with a reduction in input resistance. Three conclusions are proposed. First, RVL pacemakers have functional beta-adrenergic receptors whose activation increases their discharge rate via the intracellular production of cAMP. The effect of cAMP is due at least in part to the activation of an inward current which may be carried by a cation. Secondly, RVL neurons are in close proximity to a releasable pool of catecholamines which is susceptible to destruction by the cytotoxic agent 6-hydroxydopamine (6-OHDA). Finally it is tentatively suggested that the reduction in sympathetic tone produced by centrally acting beta-blockers could be due, at least in part, to an action of these agents on RVL pacemaker cells.
authors.affiliation: Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville 22908.
authors.forename: M K
authors.initials: MK
authors.lastname: Sun
authors.forename: P G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000320:Adrenergic Fibers / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D014439:Tyramine / Q000494:pharmacology
chemical_list: D011943:Receptors, Adrenergic, beta; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D007545:Isoproterenol; D014439:Tyramine