Zk. Krowicki et Pj. Hornby, Substance P in the dorsal motor nucleus of the vagus evokes gastric motor inhibition via neurokinin 1 receptor in rat, J PHARM EXP, 293(1), 2000, pp. 214-221
Citations number
42
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Many gastrointestinal stimuli result in gastric fundic relaxation. This inf
ormation is integrated at the interface of vagal afferents and efferents in
the dorsal vagal complex. Substance P (SP) is present in this region, and
the neurokinin, receptor (NK1R) is highly expressed in preganglionic neuron
s of the dorsal motor nucleus of the vagus (DMN). However, its functional e
ffects on vagal motor output to the stomach have not been investigated. The
refore, we determined the gastric motor effects of stereotaxic microinjecti
on of SP and selective tachykinin receptor agents into the DMN of anestheti
zed rats. Dose-related decreases in intragastric pressure and antral motili
ty were obtained on the microinjection of SP (135 and 405 pmol) into the DM
N, without cardiovascular changes. Similar decreases in intragastric pressu
re were noted after the microinjection of [Sarg(9)Met(O-2)(11)]SP (NK1R ago
nist; 135 pmol) but not senktide (NK3R agonist; 135 pmol) or vehicle. The g
astric motor inhibition evoked by SP (135 pmol) was attenuated by prior mic
roinjection of 2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-yl)-a
mine (GR203040; 1 nmol; NK1R antagonist). Vagotomy or hexamethonium (15 mg/
kg i.v.) completely abolished the gastric relaxation evoked by SP (135 pmol
) microinjected into the DMN. We conclude that SP acts on NK1R preganglioni
c cholinergic vagal neurons in the DMN, which control enteric nonadrenergic
noncholinergic motor inhibition of the fundus. The potential relevance is
that an antiemetic site of action of NK1R antagonists may be in the DMN to
prevent excitation of neurons controlling fundic relaxation, which is an es
sential prodromal component of emesis.