Role of α 2 ‐adrenoceptors in the regulation of intestinal water transport

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). Intra‐arterial infusion of noradrenaline (3, 10, 30 nmol min −1 , i.a.) and i.v. injection of the selective α 2 ‐adrenoceptor agonist UK 14,304 (1 μmol kg −1 , i.v.) increased the rate of basal fluid absorption. The effect of UK 14,304 was blocked by yohimbine (10 μmol kg −1 , i.v). However, the selective α 1 ‐adrenoceptor agonist phenylephrine (5 μmol kg −1 , i.v.) did not alter either the jejunal or ileal absorption rate. The α 2 ‐adrenoceptor antagonists yohimbine (0.3, 1.0, 3 and 10 μmol kg −1 , i.v.) and rauwolscine (10 μmol kg −1 , i.v.) decreased the basal absorption rate, while the α 1 ‐adrenoceptor antagonist prazosin (3 μmol kg −1 , i.v.) was without effect. Intracerebroventricular injection of yohimbine (3 μmol kg −1 ) caused a significant antiabsorptive effect in the jejunum but not ileum. 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. The findings provide evidence that the sympathetic nervous system exerts tonic control on intestinal fluid transport and that the effect is mainly through peripheral α 2 ‐adrenoceptors. The subtype determination of α 2 ‐adrenoceptors in modulating intestinal fluid transport was assessed by determining the effects of α 2 ‐adrenoceptor agents on intestinal fluid secretion induced by i.a. infusion of VIP (0.8 μg min −1 ). 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. EC 50 values were 0.17 μmol kg −1 in the jejunum and 0.22 μmol kg −1 in the ileum. The effect of UK 14,304 was blocked by the selective α 2A/D antagonist BRL 44408 and the non‐selective α 2 antagonist yohimbine (each 10 μmol kg −1 ). The selective α 2B/C antagonist ARC 239 (10 μmol kg −1 ) did not affect the antisecretory action of UK 14,304. It is suggested that the α 2 ‐adrenoceptors in the rat intestinal epithelium are the α 2D or α 2A ‐like subtype.British Journal of Pharmacology (1997) 120 , 892–898; doi: 10.1038/sj.bjp.0700958