Linked Life Data

7514222

Source:http://linkedlifedata.com/resource/pubmed/id/7514222

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-6-16
pubmed:abstractText
The present study was designed to characterize the antinociception produced by the administration of a muscarinic agonist, (+)-cis-methyldioxolane, into the rostral ventral medulla (RVM) of male Sprague-Dawley rats. Seven days after the implantation of 25-gauge stainless-steel guide cannulae, animals were injected with graded doses of (+)-cis-methyldioxolane, and antinociception was assessed by using the 52 degrees C hot-plate and tail-flick tests in a single-blind design. (+)-cis-Methyldioxolane produced dose-related hot-plate and tail-flick antinociception for 30 to 45 min peaking 5 to 10 min after RVM injection. The ED50 values of (+)-cis-methyldioxolane in the hot-plate and tail-flick tests were 2.4 and 1.7 nmol, respectively. Five-minute preinjections with 0.35 nmol of the muscarinic M1 receptor blocker pirenzepine competitively antagonized the antinociception produced by (+)-cis-methyldioxolane. The antinociception produced by RVM injections of the muscarinic M2 receptor blocker methoctramine was additive to the antinociceptive effects of (+)-cis-methyldioxolane when the two antinociceptive effects of (+)-cis-methyldioxolane when the two agents were combined. Twenty four-hour pretreatment of the RVM with the irreversible muscarinic receptor antagonist 4-diphenylacetoxy-N-[2-chloroethyl]-piperidine mustard blocked the antinociceptive effects of (+)-cis-methyldioxolane completely. Administration of 6 nmol of the nitric oxide synthase inhibitor L-NG-nitroarginine into the RVM competitively antagonized the antinociception produced by (+)-cis-methyldioxolane and (+)-muscarine in the hot-plate and tail-flick tests. Pretreatment with 100 nmol of L-arginine, but not D-arginine, significantly reversed the inhibitory effects of L-NG-nitroarginine on (+)-cis-methyldioxolane-produced antinociception. Pretreatment with 100 nmol of the guanylyl cyclase inhibitor methylene blue into the RVM profoundly antagonized the antinociception produced by (+)-cis-methyldioxolane. Neither buffer L-NG-nitroarginine, L-arginine-D-arginine or methylene blue altered hot-plate or tail-flick nociception when injected alone into the RVM. In contrast, either dibutyryl cyclic GMP or 8-bromo cyclic GMP, membrane-permeable cyclic GMP analogs, produced hot-plate and tail-flick antinociception when injected alone into the RVM. These data are consistent with the hypothesis that the antinociception produced by muscarinic stimulation of the RVM is mediated by an L-arginine/nitric oxide/cyclic GMP cascade.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-methyldioxolane, http://linkedlifedata.com/resource/pubmed/chemical/8-bromocyclic GMP, http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Oxidoreductases, http://linkedlifedata.com/resource/pubmed/chemical/Analgesics, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP, http://linkedlifedata.com/resource/pubmed/chemical/Dibutyryl Cyclic GMP, http://linkedlifedata.com/resource/pubmed/chemical/Dioxolanes, http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase, http://linkedlifedata.com/resource/pubmed/chemical/Muscarine, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase, http://linkedlifedata.com/resource/pubmed/chemical/Parasympathomimetics
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
699-708
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Pharmacological evidence that nitric oxide mediates the antinociception produced by muscarinic agonists in the rostral ventral medulla of rats.
pubmed:affiliation
Department of Pharmacology, University of Kentucky College of Medicine, Lexington.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.