Role of α2‐adrenoceptors in the regulation of intestinal water transport

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Abstract
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 α2‐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 α1‐adrenoceptor agonist phenylephrine (5 μmol kg−1, i.v.) did not alter either the jejunal or ileal absorption rate. The α2‐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 α1‐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 α2‐adrenoceptors. The subtype determination of α2‐adrenoceptors in modulating intestinal fluid transport was assessed by determining the effects of α2‐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. EC50 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 α2A/D antagonist BRL 44408 and the non‐selective α2 antagonist yohimbine (each 10 μmol kg−1). The selective α2B/C antagonist ARC 239 (10 μmol kg−1) did not affect the antisecretory action of UK 14,304. It is suggested that the α2‐adrenoceptors in the rat intestinal epithelium are the α2D or α2A‐like subtype. British Journal of Pharmacology (1997) 120, 892–898; doi:10.1038/sj.bjp.0700958