Relation between catecholamine-induced cyclic AMP changes and hyperpolarization in isolated rat sympathetic ganglia

摘要

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 μM) increased cyclic AMP levels by 8-100 times after 15 min incubation at 25 °C. Half-maximal stimulation occurred at about 0.03 μM. This was due to stimulation of β-receptors, since it was prevented by 1 μM-propranolol but not by 1 μM-phentolamine.3. The α-agonists phenylephrine (100 μM), dopamine (100 μM) and clonidine (1 μM) did not produce a detectable increase in ganglionic cyclic AMP. Dopamine (100 μM) was also ineffective at 37 °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 α-receptors, whereas cyclic AMP-production is induced via β-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.