PT  - JOURNAL ARTICLE
AU  - Limon-Boulez, Isabelle
AU  - Bouet-Alard, Rachel
AU  - Gettys, Tom W.
AU  - Lanier, Stephen M.
AU  - Maltier, Jean-Paul
AU  - Legrand, Chantal
TI  - Partial Agonist Clonidine Mediates α&lt;sub&gt;2&lt;/sub&gt;-AR Subtypes Specific Regulation of cAMP Accumulation in Adenylyl Cyclase II Transfected DDT1-MF2 Cells
AID  - 10.1124/mol.59.2.331
DP  - 2001 Feb 01
TA  - Molecular Pharmacology
PG  - 331--338
VI  - 59
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/59/2/331.short
4100  - http://molpharm.aspetjournals.org/content/59/2/331.full
SO  - Mol Pharmacol2001 Feb 01; 59
AB  - α2-Adrenergic receptor (α2-AR) activation in the pregnant rat myometrium at midterm potentiates β2-AR stimulation of adenylyl cyclase (AC) via Gβγ regulation of the type II isoform of adenylyl cyclase. However, at term, α2-AR activation inhibits β2-AR stimulation of AC. This phenomenon is associated with changes in α2-AR subtype expression (midterm α2A/D-AR ≫ α2B-AR; term α2B ≥ α2A/D-AR), without any change in ACII mRNA, suggesting that α2A/D- and α2B-AR differentially regulate β2-cAMP production. To address this issue, we have stably expressed the same density of α2A/D- or α2B-AR with AC II in DDT1-MF2 cells. Clonidine (partial agonist) increased β2-AR-stimulated cAMP production in α2A/D-AR-ACII transfectants but inhibited it in α2B-AR-ACII transfectants. In contrast, epinephrine (full agonist) enhanced β2-stimulated ACII in both α2A- and α2B-ACII clonal cell lines. 4-Azidoanilido-[α-32P]GTP-labeling of activated G proteins indicated that, in α2B-AR transfectants, clonidine activated only Gi2, whereas epinephrine, the full agonist, effectively coupled to Gi2 and Gi3. Thus, partial and full agonists selectively activate G proteins that lead to drug specific effects on effectors. Moreover, these data indicate that Gi3 activation is required for potentiation of β2-AR stimulation of AC by α2A/D and α2B-AR in DDT1-MF2 cells. This may reflect an issue of the amount of Gβγ released upon receptor activation and/or βγ composition of Gi3 versus Gi2.