Linked Life Data

3144283

Source:http://linkedlifedata.com/resource/pubmed/id/3144283

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1989-1-18
pubmed:abstractText
The guanine nucleotide regulatory proteins, alpha i and alpha o, coexist in a variety of tissues, including heart, brain, and adipose tissues and are ADP-ribosylated by pertussis toxin (Gilman AG, G-proteins and dual control of adenylate cyclase. Cell 26: 577-579, 1984). Previous studies in which purified G proteins were reconstituted with cell membranes and/or phospholipid vesicles have suggested that an alpha i-like protein mediates GTP-dependent inhibition of adenylate cyclase activity. However, direct studies comparing the role of alpha i and alpha o in mediating the inhibition of adenylate cyclase activity in the intact cell have not appeared. In the present study, we demonstrated that, in the intact cell, alpha o was more sensitive to ADP-ribosylation in the presence of pertussis toxin than was alpha i. The T1/2 for pertussis toxin-mediated ADP-ribosylation of alpha i was 199 +/- 10 min (mean +/- SE, N = 10) compared to 157 +/- 7 min for alpha o. The IC50 for pertussis toxin-induced ADP-ribosylation of alpha i was 158 +/- 40 pg/ml (mean +/- SE, N = 11) compared to 35 +/- 8 pg/ml for alpha o. The differences in both T1/2 and IC50 for alpha i and alpha o were statistically significant (P less than 0.001). Studies were carried out to determine whether alpha o was involved in coupling the muscarinic cholinergic receptor to inhibition of adenylate cyclase activity in intact cells. The time course and dose dependence of the pertussis toxin-induced uncoupling of the muscarinic receptor from inhibition of adenylate cyclase closely paralleled the time course and dose dependence for the ADP-ribosylation of alpha i but differed significantly (P less than 0.001) from the time course and dose dependence for the ADP-ribosylation of alpha i but differed significantly (P less than 0.001) from the time course and dose dependence of the pertussis toxin mediated ADP-ribosylation of alpha o. The T1/2 and IC50 values for the pertussis toxin-induced decrease in the inhibition of adenylate cyclase activity were 210 +/- 6 min (mean +/- SE, N = 11) and 169 +/- 25 pg/ml (mean +/- SE, N = 12), respectively, which were not significantly different from the T1/2 and IC50 for pertussis toxin mediated ADP-ribosylation of alpha i. The data are consistent with the hypothesis that, in the intact cell, a pertussis toxin-sensitive alpha i-like protein, but not alpha o, couples muscarinic receptors to inhibition of adenylate cyclase activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4549-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Differential sensitivity of alpha o and alpha i to ADP-ribosylation by pertussis toxin in the intact cultured embryonic chick ventricular myocyte. Relationship to the role of G proteins in the coupling of muscarinic cholinergic receptors to inhibition of adenylate cyclase activity.
pubmed:affiliation
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't