An adenosine A(2A) agonist injected in the nucleus of the solitary tract prolongs the laryngeal chemoreflex by a GABAergic mechanism in decerebrate piglets.
Hyperthermic prolongation of the laryngeal chemoreflex (LCR) in decerebrate piglets is prevented or reversed by GABA(A) receptor antagonists and adenosine A(2A) (Ad-A(2A)) receptor antagonists administered in the nucleus of the solitary tract (NTS). Therefore, we tested the hypothesis that enhanced GABA(A) activity and administration of the Ad-A(2A) agonist, CGS-21680, would prolong the LCR in normothermic conditions. We studied 46 decerebrate piglets ranging from 3 to 8 postnatal days of age. Focal injection into the NTS of 100 nl of 0.5 m nipecotic acid, a GABA reuptake inhibitor, significantly (P < 0.05) prolonged the LCR in normothermic conditions in 10 of 11 animals tested. Injecting 100 nl of 5-12.5 microm CGS-21680 unilaterally or bilaterally into the NTS also prolonged the LCR in normothermic conditions (n = 15), but the effect was smaller than that of unilateral injection of nipecotic acid. Systemic administration of the GABA(A) receptor antagonist, bicuculline, prevented the CGS-21680-dependent prolongation of the LCR in normothermic animals (n = 11). We conclude that thermal prolongation of the LCR depends on a thermally sensitive process or set of neurons in the NTS, which, when activated by elevated brain temperature, enhances adenosinergic and GABAergic function in the region of the NTS. These results emphasize the importance of a thermally sensitive integrative site in the dorsal medulla that, along with sites in the ventral medulla, determine the response to laryngeal chemoreflex stimulation.
Duy
Philip M
PM
Department of Physiology and Neuroscience, Dartmouth Medical School, Lebanon, NH 03756, USA.
Xia
Luxi
L
Bartlett
Donald
D
Leiter
J C
JC
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002628:Chemoreceptor Cells / Q000502:physiology; D003655:Decerebrate State / Q000503:physiopathology*; D005260:Female; D005334:Fever / Q000503:physiopathology; D058787:GABA-A Receptor Antagonists; D007830:Larynx / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology; D009557:Nipecotic Acids / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D012018:Reflex / Q000502:physiology; D017552:Solitary Nucleus / Q000187:drug effects*; D013552:Swine
D058917:Adenosine A2 Receptor Antagonists; D058787:GABA-A Receptor Antagonists; D009557:Nipecotic Acids; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D011963:Receptors, GABA-A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C030278:nipecotic acid; D000241:Adenosine; D001640:Bicuculline