Abstract

The aims of this study were to examine how the imidazoline (I)₁/alpha-2 receptor agonist moxonidine and the putative endogenous imidazoline receptor agonist agmatine might affect intestinal motility and fluid transport. The effects of moxonidine were compared with those of UK 14,304, a highly selectivealpha-2 adrenoceptor agonist with very low affinity for I₁ receptors. Moxonidine and UK 14,304 inhibited the peristaltic reflex in the isolated rat ileum. The inhibitory effects were antagonized by the selective alpha-2 adrenoceptor antagonist yohimbine and the I₁/alpha-2 antagonist efaroxan and almost completely blocked by the irreversiblealpha-2 adrenoceptor antagonist EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline), whichhas a low affinity for imidazoline receptors. Yohimbine (3 μM) and efaroxan (0.01 and 1 μM) caused parallel rightward shifts to the concentration-response curves of moxonidine and UK 14,304, yielding pK_B values corresponding to those at alpha-2 binding sites. Moxonidine induced dose-dependent proabsorptive effects in the jejunum and ileum and also reversed the secretory phase of the vasoactive intestinal peptide-induced responses. The degree of antagonism by yohimbine and efaroxan was similar against moxonidine and UK 14,304 on the proabsorptive and antisecretory effects. We conclude that the effects of moxonidine in mediating inhibition of intestinal motility and enhancing fluid transport are attributed predominantly to interaction with alpha-2 adrenoceptors. Agmatine had no effect on peristalsis but significantly decreased the rate of fluid absorption from the jejunum and ileum, an effect in contrast to moxonidine. A physiological role for agmatine in the regulation of intestinal transport remains to be clarified.