Linked Life Data

2829922

Source:http://linkedlifedata.com/resource/pubmed/id/2829922

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1988-3-24
pubmed:abstractText
The effect of the phosphodiesterase (PDE) inhibitor rolipram on the cyclic AMP responses to adenosine, histamine and combinations of these two agonists, was examined in [3H]adenine-labelled slices of guinea-pig cerebral cortex. Constant levels of [3H]-cyclic AMP were achieved within 10 min of agonist addition, both in the presence and absence of rolipram (0.1 mM). Histamine (1 mM) produced an 8-fold increase in [3H]-cyclic AMP (compared with basal) which was increased 7-fold by rolipram. The responses to adenosine (0.1 mM) and adenosine and histamine in combination were larger than that to histamine alone (46-fold or more compared with basal) but the potentiation by rolipram was much smaller (2.5-fold or less). With both agonists the effect of rolipram was dose-dependent, the steady state [3H]-cyclic AMP levels increasing 1-2-fold for a 10-fold increase in rolipram concentration. Removal of the histamine or adenosine stimulus once steady state had been reached resulted in a rapid fall in [3H]-cyclic AMP levels with a half time of less than 5 min. Rolipram (0.1 mM) did not significantly alter the initial rates of fall in [3H]-cyclic AMP levels but increased the time taken for them to return to basal levels. The findings of higher steady state levels of cyclic AMP in the presence of rolipram, together with an almost unaltered rate of cyclic AMP turnover, are consistent with an interaction of rolipram with PDE which is overcome by an increase in cyclic AMP concentration. However, the relatively smaller effects of rolipram on the higher steady levels of cyclic AMP produced by adenosine and the rather shallow dose-dependence of the PDE inhibitor on the responses to both agonists are inconsistent with a simple competitive inhibition of total PDE activity in responding cells. The results can be explained, however, by the involvement of different forms of PDE, with the rolipram-sensitive, calcium-independent form dominating at low cyclic AMP levels and the rolipram-insensitive, calcium-dependent form becoming more important when cyclic AMP levels are higher.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
715-23
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Influence of rolipram on the cyclic 3',5'-adenosine monophosphate response to histamine and adenosine in slices of guinea-pig cerebral cortex.
pubmed:affiliation
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't