Degradation of vasoactive intestinal polypeptide by rabbit gastric smooth muscle membranes

Crude membrane fractions prepared from rabbit gastric fundic muscle degraded vasoactive intestinal polypeptide (VIP) with an average specific activity of 0.96 nmol/min/mg protein at 37 degrees C, pH 7.5, and at [S]o = 0.05 mM. The relative activities towards [Leu5]enkephalin, substance P, VIP, and neurotensin were approximately 7.7, 2.0, 1.0, and 0.54, respectively. The VIP degradation was inhibited by metal chelators EDTA and o-phenanthroline. CaCl2 at 0.3-1.0 mM enhanced VIP degradation up to twofold. Phosphoramidon, captopril, and bestatin, the specific inhibitors for endopeptidase-24.11, angiotensin-converting enzyme, and aminopeptidase M, respectively, did not affect VIP degradation significantly. However, the complex mixtures of VIP fragments generated implicates action of multiple peptidases including the aforementioned three peptidases and other unidentified peptidase(s).