EFFECT OF 17-NORLEUCINE-VIP ON GASTRODUODENAL MOTILITY RELATIVE TO SERUM VIP CONCENTRATION AND BLOCKADE OF NOS

Mechanical and electrical activity in the antrum, pylorus, and duodenu m was evaluated in the conscious dog, instrumented with seven strain g auges and five platinum electrodes. 17-Norleucine-vasoactive intestina l peptide (17-N-Leu-VIP) or 17-N-Leu-VIP plus N-G-nitro-L-arginine met hyl ester (L-NAME) was injected intra-arterially close to the pylorus to identify influences of nitric oxide (NO) on effects of VIP. VIP con centration was measured by radioimmunoassay in serum samples collected from the cubital and portal veins before and up to 2 h after VIP inje ction. VIP (0.004-0.006 mg . kg(-1) . 10 min(-1)) abolished phasic con tractions in the interdigestive state for 16.8 min and in the digestiv e state for 14.4 min, whereas whole serum VIP concentration rose above 42.4 +/- 13 pmol/l. Administration of L-NAME did not significantly in fluence the effects of VIP. Aftereffects of VIP, consisting of a reduc ed motility index, lasted 33 +/- 10.6 min in the interdigestive state and 44.5 +/- 42 min in the digestive state. This VIP aftereffect in th e interdigestive state was shortened in time by the addition of L-NAME . The results overall suggest that NO release is a factor only in the aftereffects of VIP.