Linked Life Data

8996196

Source:http://linkedlifedata.com/resource/pubmed/id/8996196

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-2-10
pubmed:abstractText
The purpose of this study was to characterize the role of M2 muscarinic receptors in inhibiting relaxant effects of drugs that stimulate cyclic AMP (cAMP) accumulation in the guinea pig ileum. We investigated the ability of oxotremorine-M (oxo-M) to inhibit cAMP accumulation in the presence of agonists that stimulate adenylyl cyclase in other cells and tissues. Appreciable stimulation of cAMP (> 50% over basal levels) was achieved with forskolin and maximally effective concentrations of isoproterenol, cicaprost, prostaglandin E1, prostaglandin E2 and prostaglandin I2, with the stimulation over basal levels of cAMP being 14.9-, 2.51-, 2.45-, 2.27-, 2.28- and 1.52-fold, respectively. Moderate or no cAMP stimulation was observed with dopamine, 5-hydroxytryptamine, 5-methoxytryptamine, dimaprit, vasoactive intestinal peptide, SKF-38393, 2-chloroadenosine, CGS-21680, prostaglandin D2, secretin and vasopressin. Oxo-M (1 microM) inhibited cAMP accumulation by 35% under basal conditions. Oxo-M inhibited specific agonist-stimulated cAMP levels by 20 to 70%. However, oxo-M caused little or no inhibition of specific prostaglandin I2- and cicaprost-stimulated cAMP levels (5 and 0%, respectively). In general, there was a correlation between the abilities of the various agonists to stimulate cAMP accumulation and to cause relaxation of the isolated ileum, with an exception being cicaprost. Experiments were carried out with isolated ileum to determine whether activation of M2 receptors inhibited the relaxant effects of the various agonists. In these experiments, the ileum was first treated with N-(2-chloroethyl)-4-piperidinyl diphenylacetate to selectively inactivate M3 receptors. After this treatment phase, contractile responses to oxotremorine-M were measured in the presence of histamine and a given relaxant agent. These measurements were repeated in the presence of the M2-selective antagonist AF-DX 116. Analysis of the data showed that part of the contractile response to oxotremorine-M could be attributed to an M2-mediated inhibition of the relaxation. This M2 component of the contractile response was greatest when forskolin or isoproterenol was used as the relaxant agent. In contrast, little or no M2 response was measured in the presence of dopamine and cicaprost.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
189-99
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
M2 muscarinic receptor inhibition of agonist-induced cyclic adenosine monophosphate accumulation and relaxation in the guinea pig ileum.
pubmed:affiliation
Department of Pharmacology, College of Medicine, University of California, Irvine, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.