20 Pages

Pharmacology of Endothelins in the Gastrointestinal Tract

ByGiles A. Rae

Endothelins (ETs) are peptides with widespread biological properties, and include ET-1, ET-2, ET-3 and the mouse/rat equivalent to ET-2 vasoactive intestinal contractor. This chapter deals with the effects of ETs and sarafotoxins on different organs and tissues of the gastrointestinal tract. Aspects of ET receptors and their possible signal transduction mechanisms, sources of ETs in the gastrointestinal tract, and their effects and mechanisms of action in different organs are discussed relative to their putative physiological and/or physiopathological roles. ET-1 causes a dual effect in rabbit isolated jejunum, comprising an initial relaxation followed soon after by a slowly developing tonic contraction. Some preparations also display an inhibition of spontaneous contractions superimposed on the relaxant component of the response. ET-1 is remarkably potent in causing a sustained contraction in guinea pig gallbladder strips, being almost as potent as cholecystokinin octapeptide. ET-1 causes marked increases in perfusion pressure in the rabbit isolated perfused spleen.