Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
1997-3-5
|
| pubmed:abstractText |
GABAB receptor activation inhibits forskolin-stimulated adenylyl cyclase activity but augments noradrenaline-stimulated adenylyl cyclase activity. The present study investigated the pharmacology of these two GABAB receptor mediated responses. In a cross-chopped rat cortical slice preparation, it was confirmed that (-)baclofen inhibited forskolin-stimulated adenylyl cyclase activity and augmented noradrenaline-stimulated adenylyl cyclase activity. The potency of five further agonists was investigated (SKF97541, CGP47656, CGP44533, 3-APA and CGP44532). Of these agonists two compounds were significantly more potent as inhibitors of forskolin-stimulated adenylyl cyclase than as augmenters of noradrenaline-stimulated adenylyl cyclase activity, these were (-)baclofen (pEC50 = 6.07 +/- 0.29 and 5.04 +/- 0.17, respectively (p < 0.05)), and CGP47656 (pEC50 = 6.44 +/- 0.05 and 4.48 +/- 0.26, respectively (p < 0.05)). It is possible to explain this difference in potency by proposing that these compounds have low intrinsic efficacy, and the augmentation of noradrenaline-stimulated adenylyl cyclase has a low receptor reserve. In addition six antagonists (CGP49311A, CGP46381, CGP45024, CGP45397, CGP36742) were also tested for their ability to antagonize 10 microM (-)baclofen in these two assays. These antagonists ranged in potency as inhibitors of forskolin-stimulated adenylyl cyclase activity from CGP49311A (pEC50 = 5.45 +/- 0.30) to CGP36742 (pEC50 = 3.87 +/- 0.16). Each antagonist had similar potency in the two assays, suggesting that these two responses are mediated by pharmacologically similar receptors.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Baclofen,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-B
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0028-3908
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
35
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
703-12
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8887979-Adenylate Cyclase,
pubmed-meshheading:8887979-Animals,
pubmed-meshheading:8887979-Baclofen,
pubmed-meshheading:8887979-Brain,
pubmed-meshheading:8887979-Cyclic AMP,
pubmed-meshheading:8887979-Dose-Response Relationship, Drug,
pubmed-meshheading:8887979-Forskolin,
pubmed-meshheading:8887979-Male,
pubmed-meshheading:8887979-Norepinephrine,
pubmed-meshheading:8887979-Rats,
pubmed-meshheading:8887979-Rats, Wistar,
pubmed-meshheading:8887979-Receptors, GABA-B
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
The pharmacology of adenylyl cyclase modulation by GABAB receptors in rat brain slices.
|
| pubmed:affiliation |
Department of Pharmacology, School of Pharmacy, London, U.K.
|
| pubmed:publicationType |
Journal Article
|