Modification of spino-bulbar autonomic cholinergic systems by activation of alpha-adrenergic receptors.
Intrathecal (i.t.) injection of neostigmine was employed to activate spinal cholinergic neurons mediating a hypertensive response in freely-moving rats. Our earlier studies have demonstrated that stimulation of central alpha-adrenergic receptors inhibits the pressor response following inhibition of brain cholinesterase. Clonidine (0.5-5 micrograms) pretreatment by i.t. injection did not alter the magnitude of the pressor response to i.t. injection of neostigmine, but did significantly delay the onset of the response. Since systemic administration of clonidine abolished the pressor response to i.t. neostigmine, clonidine was administered by the intracisternal (i.c.) route to determine whether higher centers mediated the inhibitory response. In this situation, clonidine pretreatment significantly inhibited the pressor response to i.t. injection of neostigmine. I.t. injection of norepinephrine (1-10 micrograms) was more effective, but i.c. pretreatment less effective than clonidine in inhibiting the pressor response to i.t. neostigmine. In order to confirm the ascending nature of the spinal cholinergic system, hemicholinium-3 was injected i.c. to deplete medullary levels of acetylcholine. Carbachol was then injected i.t. (since carbachol is a direct-acting agonist, it is not affected by local depletion of acetylcholine). Depletion of medullary acetylcholine significantly blocked the pressor response to i.t. injection of carbachol. These findings are consistent with the concept of an ascending spinal cholinergic pressor pathway. The pressor response to activation of spinal cholinergic receptors is not sensitive to local injection of clonidine, but, the medullary cholinergic component of the system is inhibited by alpha-receptor stimulation.
Buccafusco
J J
JJ
Department of Pharmacology and Toxicology, Medical College of Georgia Augusta 30912-2300.
Magri
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D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002946:Cisterna Magna; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006426:Hemicholinium 3 / Q000494:pharmacology; D007267:Injections; D007278:Injections, Spinal; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D009388:Neostigmine / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D011950:Receptors, Cholinergic; D006426:Hemicholinium 3; D009388:Neostigmine; D002217:Carbachol; D003000:Clonidine; D009638:Norepinephrine