Role of alpha 2-adrenoceptors in the regulation of intestinal water transport.

1. The influence of the sympathetic nervous system on intestinal fluid transport by the jejunum and ileum of the anaesthetized rat was investigated under basal conditions and during active secretion induced by intra-arterial infusion of vasoactive intestinal peptide (VIP). 2. Intra-arterial infusion of noradrenaline (3, 10, 30 nmol min-1, i.a.) and i.v. injection of the selective alpha 2-adrenoceptor agonist UK 14,304 (1 mumol kg-1, i.v.) increased the rate of basal fluid absorption. The effect of UK 14,304 was blocked by yohimbine (10 mumol kg-1, i.v.). However, the selective alpha 1-adrenoceptor agonist phenylephrine (5 mumol kg-1, i.v.) did not alter either the jejunal or ileal absorption rate. 3. The alpha 2-adrenoceptor antagonists yohimbine (0.3, 1.0, 3 and 10 mumol kg-1, i.v.) and rauwolscine (10 mumol kg-1, i.v.) decreased the basal absorption rate, while the alpha 1-adrenoceptor antagonist prazosin (3 mumol kg-1, i.v.) was without effect. Intracerebroventricular injection of yohimbine (3 mumol kg-1) caused a significant antiabsorptive effect in the jejunum but not ileum. 4. Peripheral chemical sympathectomy induced by pretreating animals with 6-hydroxydopamine (150 mg kg-1, i.p., total dose) induced a trend towards impaired absorption in the jejunum and ileum. 5. The findings provide evidence that the sympathetic nervous system exerts tonic control on intestinal fluid transport and that the effect is mainly through peripheral alpha 2-adrenoceptors. 6. The subtype determination of alpha 2-adrenoceptors in modulating intestinal fluid transport was assessed by determining the effects of alpha 2-adrenoceptor agents on intestinal fluid secretion induced by i.a. infusion of VIP (0.8 microgram min-1). 7. Intravenous administration of UK 14,304 caused a dose-dependent reversal of the secretory phase of the VIP-induced response, but failed to restore fluid transport to the control level of net absorption. EC50 values were 0.17 mumol kg-1 in the jejunum and 0.22 mumol kg-1 in the ileum. 8. The effect of UK 14,304 was blocked by the selective alpha 2A/D antagonist BRL 44408 and the nonselective alpha 2 antagonist yohimbine (each 10 mumol kg-1). The selective alpha 2B/C antagonist ARC 239 (10 mumol kg-1) did not affect the antisecretory action of UK 14,304. It is suggested that the alpha 2-adrenoceptors in the rat intestinal epithelium are the alpha 2D or alpha 2A-like subtype.