Selective alpha-2 adrenoceptor agonists alter fluid and electrolyte transport in mammalian small intestine

JD Fondacaro, D Kolpak and GP McCafferty

Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pennsylvania.

The effects of the selective alpha-2 adrenoceptor agonists B-HT 920 and B-HT 933 on fluid and electrolyte transport in mammalian small intestine were assessed in vitro and in vivo. In Ussing flux chamber preparations of rabbit ileum, B-HT 920 reduces basal short-circuit current (Isc) in a concentration-dependent manner. This in vitro effect is inhibited by rauwolscine (KB = 9.7 nM) but not by prazosin. Isotope flux and ion replacement studies suggest that this decrease in Isc is due primarily to stimulation of a HCO3-dependent transport process. B- HT 920 promptly attenuates the 16,16-dimethyl prostaglandin E2 (dmPGE2)- stimulated increase in Isc and completely reverses dmPGE2-stimulated Cl secretion to absorption. Oral administration of B-HT 933 dose- dependently inhibits dmPGE2-induced enteropooling in conscious rats. This effect of B-HT 933 is likewise blocked significantly by rauwolscine but not by prazosin. Similar effects of B-HT 933 are observed on enteropooling in the pithed rat as are the effects of B-HT 920 in the conscious rat. These results indicate that selective alpha-2 adrenoceptor agonists from the azepine class of compounds have significant proabsorptive and antisecretory activities in the rabbit small intestine in vitro and in the rat intestine in vivo. This in vivo effect does not appear to be central nervous system mediated. These studies suggest that these alpha-2 adrenoceptor agonists may be useful in converting the hypersecreting mammalian small bowel to its normal absorptive state.

Volume 247, Issue 2, pp. 481-486, 11/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics