GABA(B) receptors on vagal afferent pathways: peripheral and central inhibition.
To investigate GABA(B) receptors along vagal afferent pathways, we recorded from vagal afferents, medullary neurons, and vagal efferents in ferrets. Baclofen (7-14 micromol/kg i.v.) reduced gastric tension receptor and nucleus tractus solitarii neuronal responses to gastric distension but not gastroduodenal mucosal receptor responses to cholecystokinin (CCK). GABA(B) antagonists CGP-35348 or CGP-62349 reversed effects of baclofen. Vagal efferents showed excitatory and inhibitory responses to distension and CCK. Baclofen (3 nmol i.c.v. or 7-14 micromol/kg i.v.) reduced both distension response types but reduced only inhibitory responses to CCK. CGP-35348 (100 nmol i.c.v. or 100 micromol/kg i.v.) reversed baclofen's effect on distension responses, but inhibitory responses to CCK remained attenuated. They were, however, reversed by CGP-62349 (0.4 nmol i.c.v.). In conclusion, GABA(B) receptors inhibit mechanosensitivity, not chemosensitivity, of vagal afferents peripherally. Mechanosensory input to brain stem neurons is also reduced centrally by GABA(B) receptors, but excitatory chemosensory input is unaffected. Inhibitory mechano- and chemosensory inputs to brain stem neurons (via inhibitory interneurons) are both reduced, but the pathway taken by chemosensory input involves GABA(B) receptors that are insensitive to CGP-35348.
Nerve-Gut Research Laboratory, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia.
E R
ER
Partosoedarso
R L
RL
Young
L A
LA
Blackshaw
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology; D001330:Electronic Data Processing; D005289:Ferrets / Q000502:physiology*; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000294:innervation / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D017933:Peripheral Nervous System / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D013270:Stomach / Q000294:innervation / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D002766:Cholecystokinin