Hyperpolarizing 'alpha 2'-adrenoceptors in rat sympathetic ganglia

1 Receptors mediating catecholamine-induced hyperpolarization of isolated superior cervical sympathetic ganglia of the rat have been characterized by means of an extracellular recording method.2 (-)-Noradrenaline (EC(50), 1.7 +/- 0.6 muM) produced an immediate low-amplitude (< 400 muV) hyperpolarization. The hyperpolarization was increased on removal of external Ca(2+) or on reduction of external K(+) from 6 to 2 mM. Hyperpolarization was unaffected by changing the temperature from 25 degrees to 37 degrees C.3 Hyperpolarization was also produced by the following agonists (potencies relative to (-)-noradrenaline): (-)-noradrenaline 1; (+/-)-isoprenaline 0.41; (-)-phenylephrine 0.40; (+)-noradrenaline 0.13; 2-amino-6,7-dihydroxy tetrahydronaphthalene (ADTN) 0.25; dopamine 0.1; methoxamine 0.012; amidephrine 0.0015.4 Responses were antagonized by phentolamine (1 muM) but not by (+/-)-propranolol (1 muM), haloperidol (10 muM) or alpha-flupenthixol (1 muM). This suggested that hyperpolarization was mediated solely through alpha-receptor stimulation not through stimulation of beta-receptors or dopamine-receptors.5 Dose-ratio shifts produced by phentolamine varied with different agonists. The shift increased in inverse proportion to the ability of the agonists to inhibit [(3)H]-(-)-noradrenaline uptake, suggesting that uptake of agonists limited the dose-ratio shift. Cocaine and nortriptyline reduced catecholamine-induced hyperpolarization in concentrations (10 muM and 1 muM respectively) necessary to inhibit [(3)H]-(-)-noradrenaline uptake.6 Clonidine (0.01 to 1 muM), oxymetazoline (0.01 to 1 muM) and ergometrine (0.1 to 10 muM) produced a persistent, low-amplitude hyperpolarization, as though they were partial agonists. Responses to the agonists were blocked by yohimbine (1 muM) but not be prazosin (1 muM).7 It is concluded that the adrenergic cell bodies in the ganglion were hyperpolarized through activation of the same type of alpha-receptor (;alpha(2)-receptors') as those present at adrenergic nerve terminals.