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Down‐regulation of rat brain adenosine A 1 receptors at the end of pregnancy
Author(s) -
León David,
Albasanz José Luis,
Fernández Mercedes,
Ruíz Maria Angeles,
Martín Mairena
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02220.x
Subject(s) - adenylyl cyclase , adenosine , medicine , receptor , endocrinology , adcy9 , adenosine a2b receptor , adenosine receptor , adenosine a1 receptor , gene isoform , guanosine , chemistry , gtp' , biology , biochemistry , enzyme , gene , agonist
The status of the adenosine A 1 receptor/adenylyl cyclase (A 1 R/AC) transduction pathway in rat brain was analysed at the end of pregnancy using different approaches. Pregnancy at term caused a significant decrease in the B max value obtained by saturation binding assays using [ 3 H]DPCPX as radioligand, suggesting a down‐regulation of adenosine A 1 receptor. Moreover, A 1 receptor immunodetection in pregnant rat membranes and the level of mRNA coding A 1 receptor were significantly decreased. This loss of A 1 receptor was associated with a significant increase in receptor affinity, since the K D value from the [ 3 H]DPCPX saturation curve and K i for N 6 ‐cyclohexyladenosine (CHA) were decreased in pregnant rats. Surprisingly, CHA‐mediated inhibition of adenylyl cyclase was increased, reflecting enhanced receptor responsiveness. On the other hand, immunoblotting of different αGi‐protein isoforms revealed a significant increase in αGi 3 level in membranes from pregnant rats. Pre‐incubation of membranes with anti‐αGi 3 antibody blocked the guanosine triphosphate (GTP) or CHA inhibitory effect on adenylyl cyclase in both pregnant and non‐pregnant rats, pointing to αGi 3 as the main isoform involved in the A 1 receptor response. These results suggest that, at the end of pregnancy, there is a down‐regulation of adenosine A1 receptors counterbalanced with a strengthened functionality, probably due to an increase in both αGi 3 protein and receptor affinity.