The role of luminal gastrin in the regulation of pancreatic juice secretion in preruminant calves Romuald Zabielski a , Vale ´rie Normand b , Ve ´ronique Rome ´ b , Jaroslaw Wolin ´ski c , Jean Alain Chayvialle d , Paul Guilloteau b, * a Department of Physiological Sciences, Warsaw Agricultural University, 02-766 Warsaw, Poland b Unite Mixte de Recherches sur le Veau et le Porc, UMRVP-INRA, 35 590 St. Gilles, France c The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jab lonna, Poland d INSERM U45, Hopital Edouard Herriot, 69 374 Lyon, France Received 27 October 2002; received in revised form 24 January 2004; accepted 29 January 2004 Abstract The effect of luminal gastrin on the secretion of pancreatic juice was studied in seven conscious preruminant calves employing luminal infusions of gastrin and cholecystokinin (CCK)-9 and pharmacological CCK 1 and CCK 2 receptor blocks with antagonists. The study was performed in the preprandial and prandial states. Pharmacological blocking of the CCK 2 receptor, like that of the CCK 1 receptor, resulted in reduction of pancreatic postprandial secretion and increased the duration of the prandial pattern of duodenal electrical activity. Exogenous luminal gastrin, like luminal CCK-9, enhanced the secretion of pancreatic juice proteins, though the overall effect of gastrin was weaker than that of CCK-9. The effect was inhibited by infusion of CCK 2 but also by CCK 1 receptor antagonist. In conclusion, duodenal luminal gastrin can stimulate exocrine pancreatic secretion by a mechanism that depends on CCK 2 receptors in calves. Involvement of the CCK 1 receptor in this mechanism needs further investigation. Prandial pancreatic secretory and duodenal motility cycles can be regulated by endogenous gastrin release. D 2004 Elsevier B.V. All rights reserved. Keywords: CCK; CCK 1 and CCK 2 receptors; Duodenal migrating myoelectric complex; Pancreatic polypeptide; Regulation 1. Introduction Gastrin is produced by the endocrine G-cells in the antrum and small intestine. In addition, there is an abun- dance of K-cells in the duodenum that synthesize both gastrin and cholecystokinin (CCK) [1]. According to a classical concept, gastrin exerts its biological effects fol- lowing its release into the circulating blood. However, gastrin was the first regulatory peptide detected in the lumen of the gastrointestinal tract (GI) [2]. An immunoe- lectron microscopy study by Okumiya et al. [3] revealed that in rats, gastrin is released from the duodenal G-cells into the lumen of the duodenum by a cholinergic-dependent mechanism. Following carbachol (1 AM) stimulation, lumi- nal release of gastrin exceeded the release into the blood circulation. Xu et al. [4] have shown remarkable amounts of biologically active gastrin in the duodenum in suckling pigs. In an in vitro experiment, they demonstrated that incubation of gastrin in the gastric and intestinal digestive juices of the newborn and suckling pig minimally reduced its biological activity. The biological half-life of gastrin can thus be estimated in the lumen in quarters of hours, whereas in the circulating blood, in minutes. Gastrin exerts its biological effects by acting predominantly through a CCK 2 (formerly CCK-B/gastrin) type receptor [5]. Le Dre ´an et al. [6] have demonstrated that circulating gastrin may regulate the secretion of pancreatic juice in calves probably by direct action on the pancreas. However, the presence of CCK 2 receptor mRNA was detected in the rat small intestine using a RT-PCR technique [7], and an association of mucosal CCK 2 and CCK 1 (formerly CCK- A) receptors with neural components of the calf and rat small intestine was demonstrated by immunocytochemistry [8]. These findings suggest eventual presence of an indirect mechanism controlling the exocrine pancreas at the duode- nal mucosa level by gastrin released from the G-cells. The 0167-0115/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.regpep.2004.01.010 * Corresponding author. Tel.: +33-2-2348-5355; fax: +33-2-2348-5080. E-mail address: Paul.Guilloteau@st-gilles.rennes.inra.fr (P. Guilloteau). www.elsevier.com/locate/regpep Regulatory Peptides 119 (2004) 169 – 176