Effect of muscarinic and nicotinic receptor antagonism on rat gastric motor activity.
OBJECTIVE
Our aim was to investigate whether muscarinic and nicotinic receptors mediate nitric oxide release during motor events in the rat stomach.


METHODS
Isolated rat stomach volume changes were monitored in an organ bath setup with an intragastric balloon coupled to a barostat and studied in basal conditions and during electrical vagal stimulation (EVS). In conscious rats, the intragastric pressure (IGP) was measured during test meal infusion.


RESULTS
In the presence of N(G)-nitro-L-arginine methyl ester (L-NAME; 0.1 mmol/l), EVS induced significant gastric contractions (mean +/- SEM = 0.27 +/- 0.04 ml; n = 6) that could be blocked by atropine (3 micromol/l) and hexamethonium (0.1 mmol/l). In the presence of atropine and/or hexamethonium, EVS-induced relaxations could not be blocked by L-NAME, while exogenous nitric oxide could still relax the stomach. In conscious rats, atropine (1 mg kg(-1)) initially decreased IGP, while during further distension it increased IGP. In the presence of L-NAME (30 mg kg(-1)) atropine consistently decreased IGP. L-NAME alone significantly increased IGP during the test meal infusion, but this effect was reduced in the presence of atropine.


CONCLUSIONS
These findings indicate a role for nicotinic and muscarinic receptors in the vagal-stimulation-induced activation of nitrergic nerves in the rat stomach.
Janssen
Pieter
P
AstraZeneca R&D Mölndal, Integrative Pharmacology, Gastrointestinal Biology Mölndal, Mölndal, Sweden. pieter.janssen@med.kuleuven.be
Karlsson
Lisa K C
LK
Nielsen
Maria Astin
MA
Gillberg
Per-Göran
PG
Hultin
Leif
L
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D013271:Gastric Dilatation / Q000503:physiopathology; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011312:Pressure; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D013270:Stomach / Q000187:drug effects* / Q000294:innervation / Q000502:physiology
D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase