Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two peptides derived from preproadrenomedullin, a common polypeptide precursor encoded by the AM-gene. Both AM and PAMP appear to play important roles in the regulation of vascular tone, hormone secretion from the anterior pituitary gland and adrenal function. Recent data suggest that both peptides may have some effects on blood glucose levels, food intake and gastric emptying after exogenous administration, as well as an antimicrobial effect in human colonic epithelia. Since the expression of these peptides has been found in a variety of mammalian tissues, including neuroendocrine cells in the stomach and small intestine, the aim of the present study was to investigate possible effects of PAMP and AM on intestinal functions such as motility and absorption of sugars and amino acids.

Intestinal absorption of sugars and amino acids was measured in rat jejunum with in vitro (everted rings) and in vivo techniques, as well as in monolayers of Caco-2 cells. Intestinal motility was measured by using strips of rat jejunum and guinea-pig ileum in an organ bath. Animals were anaesthetized by I.M. administration of 0.5 mg medetomidine and 10 mg ketamine per kg body weight and humanely killed at the end of the experiment. All procedures for the animal handling were performed according to the ethics committee of the University of Navarra.

The uptake of 1 mM α-methylglucoside by everted jejunal rings was significantly increased by the presence of 10^-8 M AM or PAMP. The effect was already observed after 5 min incubation and enhanced after 30 min incubation. At this exposure time, 10^-12 to 10^-8 M PAMP increased sugar absorption, 10^-10 M being the most effective concentration. Interestingly, PAMP did not show any effect at 10^-7 or 10^-6 M. AM seems to be less potent than PAMP, since no effect was found at concentrations below 10^-8 M, 10^-6 M being the most effective concentration. In contrast, the uptake of 1 mM alanine or proline was not modified by PAMP. In in vivo experiments, intraluminal infusion of 10^-7 or 10^-8 M PAMP for 15 min prior to the infusion of 1 mM α-methylglucoside for 5 min significatively reduced the absorption of this sugar. In Caco-2 cells, the presence of PAMP (10^-9-10^-7 M) for 30 or 60 min in the apical side of the monolayer significantly increased the uptake of 0.1 mM α-methylglucoside. The results of the experiments in which intestinal motility was studied showed that PAMP induced a contractile response at concentrations higher than 10^-6 M.

On the whole, our results suggest that the novel cardiovascular-active peptides PAMP and AM may have a physiological role in the modulation of intestinal motility and sugar absorption.