Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Excitation of rostral medullary pacemaker neurons with putative sympathoexcitatory function by cyclic AMP and beta-adrenoceptor agonists 'in vitro'. 215 55

The effects of isoprenaline, terbutaline and forskolin were examined on cyclic nucleotide concentrations and contractile responses in guinea-pig isolated soleus muscles. Isoprenaline and terbutaline induced rapid, concentration-related reductions in the tension and degree of fusion of subtetanic contractions of the soleus muscle. These changes were associated with increases (about 2 fold) in the levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the muscle cells. Propranolol competitively inhibited these responses. Forskolin failed to elicit a sympathomimetic response in the soleus muscles despite increasing (by about 20 fold) the intracellular concentration of cyclic AMP. Forskolin also failed to potentiate the effects induced by isoprenaline. The levels of cyclic GMP in the soleus were increased by isoprenaline (about 1.5 fold) and forskolin (about 2.5 fold). Terbutaline was without effect on cyclic GMP levels. These data suggest either that cyclic AMP is not involved as the mediator underlying beta-adrenoceptor-induced changes in contractility of slow contracting skeletal muscles or that forskolin does not stimulate the particular adenylate cyclase that leads to appropriate increases in cyclic AMP in those functional compartments associated with modulation of intracellular Ca2+ movements. Cyclic GMP is not involved in modifying changes in contractility of the soleus muscle.
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PMID:Cyclic nucleotides and contractility of isolated soleus muscle. 298 3