Linked Life Data

11259549

Source:http://linkedlifedata.com/resource/pubmed/id/11259549

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-3-22
pubmed:abstractText
Nicotinic agonists, such as epibatidine (EPI) and A-85380, when administered systemically, elicit analgesia. Intrathecal EPI also produces analgesia accompanied by nociceptive and pressor responses. Since spinal administration of drugs offers a well defined pathway connecting the site of administration with behavioral and autonomic responses, we have compared the responses to intrathecal epibatidine and A-85380 to delineate the role of nicotinic acetylcholine receptors in spinal neurotransmission. Following implantation of intrathecal catheters in rats, we monitored cardiovascular, nociceptive, and antinociceptive responses after administration of various nicotinic receptor agonists. Consistent with A-85380 displacement of epibatidine from isolated spinal cord membranes, A-85380 elicited pressor, nociceptive, and antinociceptive responses similar to EPI. Antinociception was preceded by nociception. Both antinociception and nociception were blocked by mecamylamine, methyllycaconitine, and alpha-lobeline, but dihydro-beta-erythroidine only blocked the antinociceptive response. Whereas prior administration of EPI desensitized the nociceptive and antinociceptive responses to EPI, A-85380 pretreatment only desensitized EPI-elicited nociception and not antinociception. 2-Amino-5-phosphopentanoic acid pretreatment blocked the nociceptive response to A-85380, indicating A-85380 stimulated release of glutamate onto N-methyl-D-aspartate receptors to produce the irritant response of nociception. Intrathecal phentolamine virtually abolished A-85380 antinociception, but had no effect on EPI antinociception. Hence, analgesia can be produced by stimulation of distinct spinal preterminal nicotinic receptor subtypes, resulting in the release of neurotransmitters. In the case of A-85380, these sites primarily appear to be localized on adrenergic bulbospinal terminals. Our data suggest that A-85380 and EPI act at separate preterminal spinal sites as well as on distinct nicotinic receptor subtypes to elicit an antinociceptive response at the spinal level.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
230-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
A-85380 and epibatidine each interact with disparate spinal nicotinic receptor subtypes to achieve analgesia and nociception.
pubmed:affiliation
Department of Pharmacology-0636, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA. ikhan@ucsd.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't