HYPERPOLARIZING ‘α 2 ’‐ADRENOCEPTORS IN RAT SYMPATHETIC GANGLIA

1 5-Hydroxytryptamine (5-HT)-induced membrane potential changes were recorded extracellularly from rat superior cervical ganglia (SCG) and cervical vagus nerves in vitro. 2 On the SCG, low concentrations of 5-HT (I x 10-8-3 x 10-7M) induced concentration-related hyperpolarization responses. Higher concentrations of 5-HT (I x 10-6_1 X 10-4M) induced complex responses which typically consisted of an initial hyperpolarization, followed by a depolarization and subsequent after-hyperpolarization. The depolarization, but not the initial hyperpolarization, was blocked by metoclopramide (3 x 10-5M), quipazine (1 x 10-6M) or MDL 72222 (1 x 10-5M). 3 5-HT-induced hyperpolarization of the SCG was potentiated when the amount ofcalcium chloride added to the superfusion medium was reduced from 2.5 to 0.15 mmol 1 -'. Hyperpolarization responses recorded from SCG preparations superfused with this low-calcium medium were unaffected by the substitution oflithium chloride for sodium chloride and were potentiated by the omission ofpotassium ions. Ouabain (1 x 10-3M) abolished both the hyperpolarization and the depolarization induced by 5-HT. 4 On the vagus nerve, 5-HT (1 x 10 -3 x 1I0-M) did not induce initial hyperpolarization in either normal or low-calcium Krebs-Henseleit medium. However, in the latter solution only, depolarization responses induced by 5-HT at concentrations of 1 x 10-6M or greater were followed by hyperpolarization. Both the depolarization and the post-5-HT hyperpolarization were blocked by metoclopramide (3 x 10-5M) but were unaffected by spiperone (1 x 10-7M). 5 On the vagus nerve, post-5-HT hyperpolarization responses were selectively and reversibly inhibited by ouabain, and by superfusion with Krebs-Henseleit medium that was either potassium-free or contained lithium chloride in place of sodium chloride. 7 These results demonstrate the generation in the rat SCG of a 5-HT-induced hyperpolarization response that is not mediated through 5-HT3 receptors and is unlikely to be a consequence of depolarization. In contrast, on the rat vagus nerve, the post-5-HT hyperpolarization observed in the present study had the characteristics expected of depolarization-dependent activation of a sodium ion pump.

Section: Hyperpolarization Ofthe Superior Cervical Ganglionmentioning

confidence: 79%

Origin of 5‐hydroxytryptamine‐induced hyperpolarization of the rat superior cervical ganglion and vagus nerve

Ireland

1987

“…These propranolol-resistant effects of isoprenaline were antagonized by metoclopramide and phentolamine and the pA2 values obtained (5.3 and 7.7) were identical to those obtained when clonidine was used as the agonist, indicating that isoprenaline (>0.5 gM) may activate presynaptic a-adrenoceptors. Interestingly, isoprenaline (0.5 to 1 riM) hyperpolarizes rat sympathetic ganglia prep-arations by an action which is antagonized by phentolamine but not by propranolol (Brown & Caulfield, 1979), an effect on 'a2'-adrenoceptors (Berthelson & Pettinger, 1977;Langer, 1977 (Vizi et al, 1973;Jenkins et al, 1977). Metoclopramide, by acting as an antagonist at these receptors, would prevent the inhibition, thereby augmenting the contraction.…”

Section: Discussionmentioning

confidence: 99%

Effects of Metoclopramide and Isoprenaline in the Rat Vas Deferens; Interactions With Α‐adrenoceptors

Spedding

1980

3 From these results it is concluded that metoclopramide (2.8 to 280 pM) is a presynaptic a-adrenoceptor antagonist in the rat vas deferens.4 Following,-adrenoceptor blockade with (±)-propranolol (3.3 gM), (--isoprenaline (0.47 to 14 gM) inhibited responses to field stimulation but not to phenylephrine. These propranolol-resistant effects of isoprenaline were antagonized by metoclopramide (2.8 to 280 pM) and by phentolamine (0

“…Since the hyperpolarizing effect of noradrenaline is also exaggerated under these conditions (Brown & Caulfield, 1978), it seemed possible, as suggested by Libet (1970), that the hyperpolarization might be generated by the release of endogenous catecholamines. A noradrenaline-receptor blocking agent (yohimbine: see Brown & Caulfield, 1978) was used to test this (Figure 11). At 1 jM, yohimbine nearly abolished the response to noradrenaline, reduced the initial hyperpolarization and increased the amplitude of the depolarization, but did not suppress the hyperpolarization superimposed on the on-going depolarization.…”

Section: Gangliot Hyperpolarizationmentioning

confidence: 99%

Muscarinic Receptors in Rat Sympathetic Ganglia

Brown

Fatherazi

Garthwaite

et al. 1980

Self Cite

I Potential changes in isolated superior cervical ganglia of the rat produced by muscarinic-receptor agonists were recorded by an extracellular 'air-gap' method. Depolarization was accompanied by facilitation of submaximal ganglionic transmission. 6 Muscarine (1 to 100 gM) initially reduced, then increased, the rate of 86Rb+-efflux from isolated ganglia at both 6 and 120 mM [K ]. These effects were reduced by 1 AM hyoscine.7 No consistent change in the amounts of cyclic 3',5'-guanosine monophosphate in isolated ganglia accompanying muscarinic depolarization could be detected.8 Mean against ED5o values (pM) for contracting the rat isolated ileum were: oxotremorine 0.012, methylfurmethide 0.29, (±)muscarine 0.48, pilocarpine 7.8 and AHR-602 9.9. Mean antagonist K, values (nM) were: hyoscine 0.17, atropine 0.34 and lachesine 0.27. 9 It is concluded that ganglionic muscarinic receptors are quite similar to ileal receptors in terms of agonist ED50 and antagonist K, values, and that the major difference between them lies in the greater 'efficacy' of certain agonists (pilocarpine, AHR-602 and McN-A-343) on the ganglion.