Evidence for VIP1/PACAP receptors in the afferent pathway mediating surgery‐induced fundic relaxation in the rat

• Published in: British journal of pharmacology 2000-10, Vol.131 (4), p.705-710
• Main Authors: Boeckxstaens, G E, Hollmann, M, Heisterkamp, S H, Robberecht, P, De Jonge, W J, Van Den Wijngaard, R M J G J, Tytgat, G N J, Blommaart, P J E
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gastric fundus; gastrointestinal motility; ileus; Intestine. Mesentery; nitric oxide; non‐adrenergic non‐cholinergic; vasoactive intestinal polypeptide; Vertebrates: digestive system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0703625

We previously reported activation of an inhibitory adrenergic and a non‐adrenergic non‐cholinergic (NANC) pathway during abdominal surgery relaxing the rat gastric fundus. In the present study, we investigated the possible role of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) in the NANC part of the surgery‐induced fundic relaxation. The effect of the NO biosynthesis inhibitor NG‐nitro‐L‐arginine (L‐NOARG), the non‐selective VIP receptor antagonist [D‐p‐Cl‐Phe6,Leu17]‐VIP and the selective VIP1 receptor antagonist [Acetyl‐His1,D‐Phe2,Lys15,Arg16,Leu17]‐VIP was investigated on the non‐adrenergic fundic relaxation induced by manipulation of the small intestine followed by resection of the caecum. Guanethidine partly reduced the manipulation‐induced fundic relaxation. Addition of L‐NOARG reduced this non‐adrenergic component, whereas the non‐selective VIP receptor antagonist had no significant effect. Combination of L‐NOARG and the non‐selective VIP antagonist however further reduced the relaxation to manipulation. The selective VIP1 receptor antagonist reduced the mean and maximal relaxation induced by abdominal surgery in the presence of guanethidine. When combined with L‐NOARG, the relaxation of the gastric fundus was almost completely abolished. The VIP1 receptor antagonist alone had no significant effect on the mean and maximal relaxation, but enhanced recovery of fundic tone. In conclusion, as VIP1 receptors are not present in the rat gastric fundus, these results suggest that the NANC inhibitory pathway activated during abdominal surgery involves VIP1 receptors, most likely in the afferent limb. The inhibitory neurotransmitters released at the level of the gastric fundus smooth muscle are NO and a substance different from VIP. British Journal of Pharmacology (2000) 131, 705–710; doi:10.1038/sj.bjp.0703625