In vitro and in vivo analysis of the role of Alpha-2 adrenoceptors in the regulation of gastric motility in the rat

Activation of presynaptic α2-adrenergic receptors has been known to mediate several functions of the G.I. tract. They inhibit gastrointestinal motility, gastric acid secretion and induce gastric mucosal protection. Aim: To study the effect of clonidine, oxymetazoline (α2A-adrenoceptor agonist) and ST-91 (α2B/C-adrenoceptor agonist) on electrical field stimulation (EFS)-induced contraction of isolated rat gastric fundus stripe in vitro and on insulin-induced stimulated gastric contractions in vivo. Methods: 1. Male Wistar rats (250–350g) were killed, their stomachs were removed and 3–4cm long stripes of the fundus were prepared, suspended between two electrodes in 35ml Kreb's solution at 37°C and EFS was applied. Drugs were added in a cumulative manner. 2. In anaesthetized rats the gastric motility was measured by the balloon method. To stimulate gastric motility insulin (i.v) was given. Results: 1. Clonidine, oxymetazoline and ST-91 in dose of (100–10000nM) inhibited the EFS-induced contractions in a concentration dependent manner. 2. Idazoxan, a non selective α2-adrenoceptor antagonist (1000–10000nM) reversed the inhibitory effect of clonidine and ST-91, but not that of oxymetazoline. ARC-239 and BRL 44408(1000–10000nM resp.), (selective α2B- and α2A-adrenoceptor antagonists, respectively) significantly reversed the inhibitory effect of clonidine and ST-91. 3. Injection of clonidine (1.9–3.8µmol/kgi.v), oxymetazoline (0.1–3.4µmol/kg i.v) and ST-91 (2,2µmol/kg i.v) inhibited the gastric motility stimulated by insulin. 4. The effect of clonidine was antagonized by yohimbine (5µmol/kgi.v), BRL44408 (3µmol/kgi.v) and prazosin (α1- and α2B-adrenoceptor antagonist) (0.28µmol/kgi.v), while the inhibitory effect of oxymetazoline was unaffected by these antagonists. Conclusion: 1. Besides α2A-adrenoceptors the 2B-subtype is also likely to be involved in inhibition of gastric motorα activity both in vivo and in vitro. 2. Oxymetazoline-induced inhibition of gastric motility may be mediated at least partly by a non-α-adrenoceptor-mediated mechanism.