The calcitonin gene related peptide (CGRP) is widely distributed in the ent
eric nervous system and gut afferents. Its role in normal digestion and abs
orption is not characterised. This study is conducted to elucidate whether
CGRP regulates amino acid absorption in the small intestine. In in vivo exp
eriments using the single-pass perfusion technique, intravenous infusion of
CGRP (250-750 pmol/kg-min) reduced alanine absorption by 35-40%. The effec
ts were completely blocked by the antagonist hCGRP (8-37). Moreover, intrav
enous infusion of CGRP antagonist blocked the inhibitory effect of intralum
inal capsaicin perfusion on alanine absorption. Similarly, intracerebral in
jection of CGRP decreased alanine absorption, an effect which was reduced b
y vagotomy. In vitro experiments using isolated jejunal strips showed that
CGRP reduced alanine absorption in a dose-dependent manner. At 6 pM, CGRP d
ecreased alanine absorption by 33%. Similarly, CGRP reduced the absorption
of proline and taurine by 20 and 11.5%, respectively. Kinetic studies revea
led that CGRP reduces alanine influx into intestinal epithelial cells by in
hibiting the affinity of the carriers. It is demonstrated that CGRP is invo
lved in the regulation of jejunal amino acid absorption through intrinsic (
enteric) and extrinsic (central) neural mechanisms. (C) 2000 Elsevier Scien
ce B.V. All rights reserved.