Vagal CCK and 5-HT(3) receptors are unlikely to mediate LPS or IL-1beta-induced fever.
Previous studies suggested that peripheral immune mediators may involve intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have therefore investigated a possible role for vagal CCK-A and 5-HT(3) receptors in the febrile response after intraperitoneal human recombinant interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate (100 or 150 microgram/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In other experiments, rats were treated with either antagonists to the 5-HT(3) receptor (ondansetron HCl; 100 microgram/kg) or the CCK-A receptor (L-364,718, 100 or 200 microgram/kg) in combination with LPS or IL-1beta. CCK administration caused a short-lived hypothermia, but interference with the action of endogenous CCK at CCK-A receptors was without effect on IL-1beta- or LPS-induced fever. Neither activation of 5-HT(3) receptors nor blockade of 5-HT(3) receptors affected body temperature or LPS fever. Taken together, our data support the idea that vagal afferents responsive to pyrogenic cytokines may be different from those responsive to CCK or 5-HT.
Martin
S M
SM
Mt. Saint Vincent University, Halifax, Nova Scotia B3M 2J6.
Wilson
B C
BC
Chen
X
X
Takahashi
Y
Y
Poulin
P
P
Pittman
Q J
QJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D020109:Devazepide / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D014630:Vagus Nerve / Q000737:chemistry / Q000378:metabolism*
D006727:Hormone Antagonists; D007375:Interleukin-1; D008070:Lipopolysaccharides; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017294:Ondansetron; C045918:2-methyl-5-HT; D020109:Devazepide; D012844:Sincalide