The tachykinin NK1 receptor antagonist GR205171 prevents vagal stimulation-induced retching but not neuronal transmission from emetic vagal afferents to solitary nucleus neurons in dogs.
Tachykinin NK1 receptor antagonists injected into the medulla oblongata are known to abolish vomiting induced by vagal afferent stimulation. Emetic vagal afferents have been shown to synapse with neurons in the medial solitary nucleus (mNTS), which suggests that substance P is a transmitter in the synapse. To examine this possibility, the effects of GR205171, an NK1 receptor antagonist, on retching and mNTS neuronal responses to the stimulation of abdominal vagal afferents were investigated in decerebrate dogs. GR205171 (0.05-0.7 mg kg-1, i.v.) abolished retching induced by either vagal or mNTS stimulation within 5 min. Firing of mNTS neurons in response to pulse-train and sustained vagal stimulation did not change even after the abolition of retching. Similarly, GR205171 did not have any effects on mNTS evoked potentials induced by pulse-train vagal stimulation. In about 20% of mNTS neurons, the peak firing frequency was facilitated to about 150% with repetitive pulse-train vagal stimulation. This facilitation remained even after the abolition of retching. Administration of GR205171 (1 mg ml-1, 30 microliters) into the 4th ventricle abolished retching, with latencies in excess of 120 min These results suggest that substance P does not participate in synaptic transmission between emetic vagal afferents and mNTS neurons in dogs.
Fukuda
H
H
Department of Physiology, Kawasaki Medical School, Kurashiki, Japan.
Koga
T
T
Furukawa
N
N
Nakamura
E
E
Shiroshita
Y
Y
D000818:Animals; D004285:Dogs; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*; D014839:Vomiting / Q000517:prevention & control*
D010880:Piperidines; D018039:Receptors, Tachykinin; D013777:Tetrazoles; C103207:vofopitant