Relation between catecholamine-induced cyclic AMP changes and hyperpolarization in isolated rat sympathetic ganglia.
1. The effect of catecholamines on cyclic adenosine 3'5'-monophosphate (cyclic AMP) production in isolated rat superior cervical ganglia has been measured under experimental conditions in which they also produce ganglion hyperpolarization.2. (+/-)Isoprenaline (1 muM) increased cyclic AMP levels by 8-100 times after 15 min incubation at 25 degrees C. Half-maximal stimulation occurred at about 0.03 muM. This was due to stimulation of beta-receptors, since it was prevented by 1 muM-propranolol but not by 1 muM-phentolamine.3. The alpha-agonists phenylephrine (100 muM), dopamine (100 muM) and clonidine (1 muM) did not produce a detectable increase in ganglionic cyclic AMP. Dopamine (100 muM) was also ineffective at 37 degrees C in the presence of 10 mM-theophylline.4. Exogenous cyclic AMP (0.01-1 mM) hyperpolarized the ganglion. This effect was replicated by other adenosine compounds, most effectively by adenosine and by adenosine 5'-monophosphate, and was antagonized by theophylline. Dibutyryl cyclic AMP was weaker than cyclic AMP.5. Neither theophylline nor the non-xanthine phosphodiesterase inhibitor, Ro 20-1724, enhanced the hyperpolarizing actions of noradrenaline or dopamine.6. Since catecholamine-induced hyperpolarization of the isolated rat ganglion is induced via alpha-receptors, whereas cyclic AMP-production is induced via beta-receptors, it is concluded that cyclic AMP is unlikely to mediate the hyperpolarization. The effect of exogenous cyclic AMP may be due to an action on external adenosine-receptors.
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000494:pharmacology; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology; D013806:Theophylline / Q000494:pharmacology
D002395:Catecholamines; D011941:Receptors, Adrenergic; D013806:Theophylline; D000242:Cyclic AMP