Peptidergic component of non-adrenergic non-cholinergic relaxation of the rat gastric fundus.

Findings from a number of studies suggest that non-adrenergic non-cholinergic (NANC) relaxation of the rat gastric fundus includes a peptidergic component, which seems to be mediated by vasoactive intestinal polypeptide (VIP). The aim of the present study was to define the role of this peptide in the high-frequency, electrical field stimulation (EFS)-induced response of rat fundus strips. Longitudinal muscle strips of the rat gastric fundus were mounted under isotonic conditions (1-g load) between platinum electrodes inside 5-ml organ baths containing Krebs solution maintained at 37°C and bubbled with O2/CO2 95:5%. The Krebs solution contained 1 µM atropine and 5 µM guanethidine, to obtain NANC conditions, and 0.1 µM U46619, to increase strip tone. In a first series of experiments, the strips were exposed to VIP (0.3 nM–0.3 µM; 2-min incubation). Studies were then conducted to identify the effects of α-chymotrypsin (1 U/ml) and anti-VIP serum(1:100) on the inhibitory response evoked by 13 Hz EFS. All relaxant responses were expressed as both amplitudes and areas under thecurves (AUC) and the results were evaluated by means of Student’s paired and unpaired t test. VIP (0.3 nM–0.3 µM) induced concentration-dependent relaxations. It was possible to plot two different concentration-response curves, one based on amplitude and the second on the AUC of each relaxation. VIP was approximately 15 times more potent in inducing the amplitude than the AUC of the relaxant responses. α-Chymotrypsin (1 U/ml) and anti-VIP serum (1:100) significantly reduced the AUCs with respect to pre-treatment controls, but neither had any effect on the amplitude. These data clearly indicate that a peptidergic component is present in the NANC inhibitory response of the rat gastric fundus to high-frequency EFS and is mainly involved in maintenance of the response.