Stimulatory pathways and sites of action of intrathecally administered nicotinic agents.
Intrathecal (i.t.) administration of nicotinic agonists to rats elicits a receptor-mediated pressor response, a heart rate increase and irritation-nociceptive behavior. We examined the stimulatory pathways and sites of action of spinally administered nicotinic agonists. The thoracic region appears more sensitive to nicotine-elicited pressor actions than the lumbar or cervical regions of the spinal cord. Nicotinic receptors evoking a nociceptive response appear to be located over an area extending from the lumbar rostrally to the thoracic region. Similar to the pressor response, the thoracic spinal cord is the most sensitive region to nicotine in producing the heart rate increase. The cervical region is the least responsive to nicotine, suggesting sites of actions caudal to the brain stem. Intravenous infusion of trimethaphan inhibited the nicotine-elicited pressor response and tachycardia without affecting the irritation response. This suggests that the cardiovascular responses to spinal nicotinic agonists result from enhanced sympathetic outflow. Intrathecal morphine and MK-801 block spinal nicotine-elicited irritation and tachycardia but not the pressor response, indicating that pressor and irritation responses involve independent receptor-mediated pathways. Tachycardia may be associated with the irritation response. In contrast to nicotine, both pressor and irritation responses to cytisine were blocked by morphine with no effect on heart rate. Spinal transection at the T1-2 level eliminated the nociceptive response to nicotine but not the pressor response. Cytisine responses were similar to nicotine; however, cytisine was significantly less potent as a pressor agent in the transected compared with intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Khan
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IM
Department of Pharmacology, University of California, San Diego, La Jolla 92093.
Taylor
P
P
Yaksh
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TL
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006426:Hemicholinium 3 / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011807:Quinolizines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014294:Trimethaphan / Q000494:pharmacology; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D006426:Hemicholinium 3; D009538:Nicotine; D018722:Nicotinic Agonists; D011807:Quinolizines; D014294:Trimethaphan; C004712:cytisine; D000093843:Quinolizidine Alkaloids