Effects of 3,4-diaminopyridine and tetraethylammonium on the pre- and post-junctional alpha-adrenoceptor mediated inhibitory actions of noradrenaline in the guinea-pig ileum

Abstract

The effects of potassium channel blockers, 3,4-diaminopyridine (DAP) and tetraethylammonium (TEA) were studied on the pre- and post-junctional alpha 2-adrenoceptor mediated effects of noradrenaline in the guinea-pig proximal ileum. Both DAP (4 to 500 mumol l-1) and TEA (0.3 to 3 mmol l-1) transiently increased the basal tension of the ileum. However, DAP also increased the amplitude of the smooth muscle twitches evoked by transmural nerve stimulation, whereas TEA marginally depressed them. Atropine (2 mumol l-1) antagonized the contractions induced by DAP but did not affect the similar effects of TEA. On the other hand, DAP restored the smooth muscle twitches depressed by atropine, while TEA did not. DAP, in a concentration-dependent manner, reduced or abolished the prejunctional inhibitory alpha 2-adrenoceptor mediated effect of noradrenaline, whereas TEA (up to 3 mmol l-1) was almost ineffective. The postjunctional inhibitory alpha 2-adrenoceptor mediated effect of noradrenaline was attenuated even at the smallest TEA concentration used (0.3 mmol l-1) and its postjunctional stimulatory alpha 1-adrenoceptor mediated effect was unmasked. However, DAP, was only marginally effective, even at the highest concentrations used (100 and 500 mumol l-1). From these results it would appear that in both the pre- and post-junctional inhibitory alpha 2-adrenoceptor mediated actions of noradrenaline in the guinea-pig ileum the primary step might be an increased potassium conductance. However, the potassium channels on the neuronal and the smooth muscle membrane have different sensitivities to DAP and TEA.