Role of galanin receptor 1 in gastric motility in rat.
Galanin actions are mediated by distinct galanin receptors (GAL-R), GAL-R1, -R2 and -R3. We investigated the role of GAL-R1 in gastric motility and the expression of GAL-R1 in the rat stomach. In vivo, in urethane-anaesthetized rats, galanin (equipotent for all GAL-Rs) induced a short inhibition of gastric motility, followed by increase in tonic and phasic gastric motility; the latter was significantly reduced by the GAL-R1 antagonist, RWJ-57408. Galanin 1-16 (high affinity for GAL-R1 and -R2) induced a long-lasting decrease of intragastric pressure, which was not modified by RWJ-57408. In vitro, galanin and galanin 1-16 induced increase of intragastric pressure that was not affected by RWJ-57408. Tetrodotoxin (TTX) did not suppress the galanin excitatory effect, whereas the effect of galanin 1-16 on gastric contraction was increased by TTX- or N-nitro-L-arginine, an inhibitor of nitric oxide synthase. GAL-R1 immunoreactivity was localized to cholinergic and tachykinergic neurons and to neurons immunoreactive for nitric oxide synthase or vasoactive intestinal polypeptide. This study suggests that an extrinsic GAL-R1 pathway mediates the galanin excitatory action, whereas an extrinsic, non GAL-R1 pathway is likely to mediate the galanin inhibitory effect in vivo. GAL-R1 intrinsic neurons do not appear to play a major role in the control of gastric motility.
CURE Digestive Diseases Research Center, Division of Digestive Diseases, VAGLAHS, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.
S
S
Guerrini
H E
HE
Raybould
L
L
Anselmi
A
A
Agazzi
E
E
Cervio
J R
JR
Reeve
M
M
Tonini
C
C
Sternini
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019004:Galanin / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044091:Receptor, Galanin, Type 1 / Q000819:agonists / Q000502:physiology*
D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; C062019:galanin (1-16); D019004:Galanin