Excitation of dorsal motor vagal neurons evokes non-nicotinic receptor-mediated gastric relaxation.
Vagal stimulation results in both gastric motor excitatory and non-adrenergic non-cholinergic (NANC) inhibitory responses. The NANC pathway involves preganglionic cholinergic neurons, which act through nicotinic receptors to ultimately evoke gastric smooth muscle relaxation via release of nitric oxide (NO) and other neurotransmitters. Within the dorsal motor nucleus of the vagus (DMN), some preganglionic neurons also contain NO synthase. The NO synthase-containing neurons innervate the gastric fundus where adaptive relaxation occurs. This study tests the hypothesis that chemical stimulation of vagal motor neurons in animals, in which nicotinic receptors are blocked, evokes an NO-dependent gastric relaxation. A cell body excitant, N-methyl-D-aspartate (NMDA, 0.03-3 nmol), was microinjected into the DMN in anesthetized rats while recording intragastric pressure (IgP). The first group received NMDA before and after administration of a ganglionic blocker, hexamethonium bromide (15 mg/kg, i.v.) and atropine (1.0 mg/kg). Significant dose-dependent increases in IgP and gastric motility occurred before hexamethonium after the 0.3 and 3 nmol doses of NMDA. After hexamethonium, 0.3 and 3 nmol NMDA evoked significant decreases in IgP. A second group of rats was hexamethonium-pretreated and received NMDA microinjection into the DMN before and after an NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (10 mg/kg, i.v.). The NMDA-evoked decrease in IgP was completely abolished by the NO synthase inhibitor. These data support the novel idea that NO synthase-containing preganglionic neurons mediate gastric relaxation that is independent of nicotinic receptors.
Krowicki
Z K
ZK
Department of Pharmacology and Neuroscience Center of Excellence, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
Sivarao
D V
DV
Abrahams
T P
TP
Hornby
P J
PJ
D000818:Animals; D019540:Area Under Curve; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects; D018698:Glutamic Acid / Q000008:administration & dosage; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008845:Microinjections; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000008:administration & dosage; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D018733:Nicotinic Antagonists; D009569:Nitric Oxide; D018738:Hexamethonium; D018698:Glutamic Acid; D016202:N-Methylaspartate; D001285:Atropine