DEGRADATION OF VASOACTIVE INTESTINAL POLYPEPTIDE BY RABBIT GASTRIC SMOOTH-MUSCLE MEMBRANES

Crude membrane fractions prepared from rabbit gastric fundic muscle de graded vasoactive intestinal polypeptide (VIP) with an average specifi c activity of 0.96 nmol/min/mg protein at 37-degrees-C, pH 7.5, and at [S]0 = 0.05 mM. The relative activities towards [Leu5]enkephalin, sub stance P, VIP, and neurotensin were approximately 7.7, 2.0, 1.0, and 0 .54, respectively. The VIP degradation was inhibited by metal chelator s EDTA and o-phenanthroline. CaCl2 at 0.3-1.0 mM enhanced VIP degradat ion up to twofold. Phosphoramidon, captopril, and bestatin. the specif ic inhibitors for endopeptidase-24.11, angiotensin-converting enzyme, and aminopeptidase M. respectively, did not affect VIP degradation sig nificantly. However, the complex mixtures of VIP fragments generated i mplicates action of multiple peptidases including the aforementioned t hree peptidases and other unidentified peptidase(s).