Neurokinetic and myokinetic effects of the peptide xenin on the motility of the small and large intestine of guinea pig.
The effects of xenin 25, a peptide of the neurotensin/xenopsin family, were examined on the motility of the guinea pig jejunum and colon in vitro. In the jejunum, xenin induced a biphasic response: first a small relaxation and then a large contraction. In the colon, xenin induced relaxation. The tenia coli was contracted. Deletion or amidation of the C-terminal leucine inactivated xenin. A peptide sequence of 16 C-terminal amino acids was necessary to elicit a full response in the jejunum, whereas in the colon, the potencies of all fragments of xenin 25, including the 6 C-terminal amino acid sequence (xenin 6), were not significantly different from that of xenin 25. In the jejunum, contraction was abolished or reduced by tetrodotoxin, by atropine, by met-enkephalin, by antagonists to the tachykinin receptors NK1 and NK2 and by the P2-purinoceptor antagonist suramin. L-NNA, phentolamine, methysergide, hexamethonium and apamin had no effect. In the colon, all actions of xenin were tetrodotoxin-resistant; the potency of xenin to relax was reduced by apamin and suramin. The actions of xenin on small and large bowel were attenuated by the neurotensin receptor antagonist SR 48692. The xenin analog neurotensin was significantly less potent than xenin 25 in contracting the jejunum and more potent than xenin 25 in relaxing the colon. We conclude that xenin exerts excitatory effects on a neuronal subtype receptor in the jejunum, with participation of muscarinic, purinergic and tachykinin-related mechanisms. Xenin exerts relaxing effects on the colon by interaction with a myokinetic subtype receptor involving Ca(++)-dependent K+ channels and the P2-purinoceptor.
Feurle
G E
GE
DRK Krankenhaus Neuwied, University of Bonn, Germany.
Klein
A
A
Hamscher
G
G
Metzger
J W
JW
Schuurkes
J A
JA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D007422:Intestines / Q000187:drug effects*; D008297:Male; D009496:Neurotensin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*
D010455:Peptides; C077659:xenin 25; D009496:Neurotensin