Norepinephrine and alpha-2 adrenoceptors modulate active ion transport in porcine small intestine

The effects of norepinephrine (NE) were examined on active ion transport in the porcine distal jejunum under base-line conditions and after electrical transmural stimulation (ETS). Serosal administration of NE decreased basal short-circuit current across sheets of muscle-stripped jejunal submucosa- mucosa in vitro. These effects were absent in tissues pretreated with the neuronal conduction blocker, tetrodotoxin. NE stimulated net Na secretion in tissues which displayed basal net Na and Cl absorption and increased net Cl absorption in tissues which displayed net Na absorption and Cl secretion under base-line conditions. Moreover, NE inhibited short-circuit current elevations produced by ETS (300 pulses at 10 Hz, 0.5 msec pulse duration, 2.8 mA cm^-2), the ganglionic stimulant dimethylphenyl-piperazinium or the gut peptide neurotensin. In contrast, NE did not alter mucosal responses to the directly acting secretogogues forskolin and carbachol. The inhibitory action of NE on mucosal responses evoked by ETS were selectively antagonized by the alpha adrenoceptor blockers phentolamine and yohimbine. Moreover, the selective alpha-2 adrenoceptor agonists p-aminoclonidine, UK-14,304 and oxymetazoline and the NE releasing agent tyramine mimicked the inhibitory effects of NE on ETS-evoked mucosal responses. Desipramine, a blocker of neuronal NE uptake, produced a 1000-fold increase in the potency of NE at concentrations less than 1 nM. These results suggest that NE modulates active ion transport by interacting with alpha-2 adrenoceptors located on submucosal neurons of the porcine small intestine.