Effects of histamine H2-receptor antagonists on human plasma levels of calcitonin gene-related peptide, substance P and vasoactive intestinal peptide

Abstract

Abstract The effects of the histamine H2-receptor antagonists (H2-antagonists), ranitidine, nizatidine, cimetidine and famotidine, on plasma levels of gastrointestinal peptides, calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP) was investigated with respect to regulation of gastric mucosal blood flow, in healthy volunteers. H2-Antagonists or placebo was orally administered to five healthy male volunteers. Venous blood samples were taken before and after drug administration. The levels of plasma gastrointestinal peptides were determined by enzyme immunoassay. The administration of ranitidine and nizatidine caused significant increases in plasma CGRP and SP levels at 30 to 120 min compared with the placebo group. Peak plasma CGRP levels (39.8 ± 3.1 and 40.6 ± 3.6 pg mL−1) were achieved 60 min after administration of ranitidine and nizatidine, respectively. Maximum plasma SP levels (21.3 ± 5.2 and 22.8 ± 4.2 pg mL−1) were reached 60 min after administration of ranitidine and nizatidine, respectively. However, all H2-antagonists did not alter the levels of VIP. The released CGRP and SP by ranitidine and nizatidine administration may produce a gastroprotective effect, increase mucosal blood flow, and inhibit acid secretion in the gastrointestinal tract.