AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 6 1004-G1011, Copyright © 1995 by American Physiological Society
Responses of ferret lower esophageal sphincter to 5-hydroxytryptamine: pathways and receptor subtypes
L. A. Blackshaw, V. Nisyrios and J. Dent
Royal Adelaide Hospital, Australia.
In urethananesthetized ferrets, basal lower esophageal sphincter pressure
(LESP) was unaffected by the 5-hydroxytryptamine3 (5-HT3) receptor
antagonist granisetron (0.5 mg/kg) or by greater splanchnic nerve section
(GSX), but increased after bilateral vagotomy. Peripheral vagal nerve
stimulation caused LES relaxation, often followed by a brief contraction
and a prolonged inhibition of LESP. Close intra-arterial injection of 5-HT
(5-100 micrograms) had a biphasic effect on LESP, with a brief drop
followed by a prolonged increase. Granisetron (0.5 mg/kg i.v.) abolished
the initial relaxation and revealed an earlier peak of excitation. This was
not influenced by subsequent vagotomy and GSX. In a series of eight
additional experiments (series 2), granisetron was given after vagotomy and
GSX. In series 2, 5-HT-induced relaxation was unaffected by vagotomy but
was significantly reduced after GSX and was further reduced after
granisetron, indicating that 5-HT3 receptor mechanisms may lie on a
sympathetic neural pathway. Vagotomy had no effect on the excitatory
component. GSX had no effect on the amplitude of excitation, but reduced
its latency. Granisetron had no further effect on excitation in series 2.
In a separate series of 13 experiments (series 3), the excitatory component
of the LES response to 5-HT was abolished by ketanserin (2.5 mg/kg i.v.) ,
after which only relaxation occurred. Both 5-HT2 and 5-HT3 antagonists in
combination abolished all effects of 5-HT on LESP. Atropine (400
micrograms/kg i.v., n = 7) had no effect on 5-HT-induced LES
responses.(ABSTRACT TRUNCATED AT 250 WORDS)
