Alpha 2-adrenoceptor antisecretory responses in the rat jejunum

1. Addition of noradrenaline (5 microM), UK-14,304 (0.1 microM) or phenylephrine (100 microM) to the serosal surface of sheets of rat jejunum mounted in Ussing type chambers decreased resting transepithelial short circuit current (SSC). These responses were inhibited by the selective alpha 2-adrenoceptor antagonist idazoxan (0.5-5.0 microM) but were not significantly affected by the alpha 1-adrenoceptor antagonist corynanthine (100 microM). 2. All three agonists caused a dose-related reduction of SSC which had been elevated by prior addition of theophylline (4 mM). UK-14,304 was 8.1 times more potent than noradrenaline and 76.2 times more potent than phenylephrine. Idazoxan (10 nM-1 microM) caused rightward, parallel displacements of the concentration-response curves for noradrenaline and UK-14,304; PA2 values were 7.87 and 8.02 respectively. Dose-response curves to noradrenaline were unaffected by prazosin (1 microM). 3. The reduction by noradrenaline (10 microM) of SCC which had been elevated by theophylline (4 mM) was not significantly affected by tetrodotoxin (5 microM), suggesting that noradrenaline reduces SCC in rat jejunum via a direct mucosal mechanism. 4. The resting SCC was markedly reduced in chloride-free PSS and under these conditions, noradrenaline did not elicit any further fall in SCC. In bicarbonate-free physiological salt solution (PSS) the resting SCC and the noradrenaline-induced fall in SCC were not significantly different from those in normal PSS. It is concluded that the decrease in SCC observed with noradrenaline, UK-14,304 and phenylephrine is mediated via stimulation of postjunctional alpha 2-adrenoceptors.