Effects of microdialyzed oxotremorine, carbachol, epibatidine, and scopolamine on intraspinal release of acetylcholine in the rat.
Intrathecally administered cholinergic agonists such as oxotremorine (muscarinic), carbachol (mixed nicotinic and muscarinic agonist), and epibatidine (nicotinic) have all been shown to reduce nociception in behavioral studies. Thus, there is substantial evidence for a role of acetylcholine (ACh) in the control of nociception in the spinal cord, but the mechanisms regulating ACh release are not known. The present study was initiated to establish a rat model to study which mechanisms are involved in the control of ACh release. Spinal microdialysis probes were inserted intraspinally at the C1-C5 spinal level in isoflurane-anesthetized rats. The probes were perfused with Ringer's solution containing 10 microM neostigmine to prevent degradation of ACh. Oxotremorine, carbachol, epibatidine, and scopolamine, dissolved in Ringer's solution, were administered intraspinally via dialysis and 30 microliter/10-min samples of dialysate were collected for HPLC analysis of ACh content. The release of ACh was found to be constant in the control (Ringer's only) situation during the experimental period of 150 min. Oxotremorine (100-1000 microM), carbachol (1 mM), and epibatidine (50-5000 microM) enhanced but scopolamine (50-200 nM) decreased the intraspinal release of ACh. Oxotremorine (ED(50) = 118 microM) and epibatidine (ED(50) = 175 microM) were found to produce a dose-dependent increase of ACh release. Cholinergic agonists caused an increase of intraspinal ACh and the antagonist scopolamine caused a decreased release of ACh. The data do not support an autoreceptor function of either nicotinic or muscarinic receptors in the spinal cord, contrary to what has been observed in the brain.
Höglund
A U
AU
Department of Physiology, Division of Comparative Medicine, Uppsala University, Uppsala, Sweden. urban.hoglund@bmc.uu.se
Hamilton
C
C
Lindblom
L
L
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017551:Microdialysis; D010095:Oxotremorine / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018679:Cholinergic Agonists; D011725:Pyridines; D010095:Oxotremorine; D002217:Carbachol; D012601:Scopolamine; C082748:epibatidine; D000109:Acetylcholine