TY - JOUR
T1 - Coupling of a Single Adenylate Cyclase to Two Receptors
T2 - Adenosine and Catecholamine
AU - Tolkovsky, Aviva M.
AU - Levitzki, Alexander
PY - 1978
Y1 - 1978
N2 - A detailed kinetic analysis on the rate of activation of adenylate cyclase by 1-epinephrine and by adenosine, separately and combined, was performed. Both ligands were found to induce the activation of adenylate cyclase to its permanently active state in the presence of guanylyl imidodiphosphate (GppNHp). The activation followed strictly first-order kinetics. On the basis of these experiments, it was found that all of the enzyme pool can be activated by the β-adrenergic receptor, but only 60 to 70% of the enzyme can also be activated by an adenosine receptor. The remaining 30 to 40% cannot be activated by adenosine. While previous experiments have led us to conclude that the epinephrine receptor is uncoupled from the adenylate cyclase, it seems that the adenosine receptor is either precoupled to the enzyme or forms a long-lived intermediate of adenosine-receptor-enzyme complex. From the pattern of enzyme activation by the two ligands and GppNHp, it may be concluded that the two ligands, adenosine and the β-agonist, activate the adenylate cyclase through a common guanyl nucleotide regulatory site. This assertion is supported by the finding that both adenosine and 1-epinephrine, in the presence of GTP, induce the reversal of the permanently active state, irrespective by which pathway the enzvme was activated.
AB - A detailed kinetic analysis on the rate of activation of adenylate cyclase by 1-epinephrine and by adenosine, separately and combined, was performed. Both ligands were found to induce the activation of adenylate cyclase to its permanently active state in the presence of guanylyl imidodiphosphate (GppNHp). The activation followed strictly first-order kinetics. On the basis of these experiments, it was found that all of the enzyme pool can be activated by the β-adrenergic receptor, but only 60 to 70% of the enzyme can also be activated by an adenosine receptor. The remaining 30 to 40% cannot be activated by adenosine. While previous experiments have led us to conclude that the epinephrine receptor is uncoupled from the adenylate cyclase, it seems that the adenosine receptor is either precoupled to the enzyme or forms a long-lived intermediate of adenosine-receptor-enzyme complex. From the pattern of enzyme activation by the two ligands and GppNHp, it may be concluded that the two ligands, adenosine and the β-agonist, activate the adenylate cyclase through a common guanyl nucleotide regulatory site. This assertion is supported by the finding that both adenosine and 1-epinephrine, in the presence of GTP, induce the reversal of the permanently active state, irrespective by which pathway the enzvme was activated.
UR - http://www.scopus.com/inward/record.url?scp=0018126502&partnerID=8YFLogxK
U2 - 10.1021/bi00611a021
DO - 10.1021/bi00611a021
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C2 - 698198
AN - SCOPUS:0018126502
SN - 0006-2960
VL - 17
SP - 3811
EP - 3817
JO - Biochemistry
JF - Biochemistry
IS - 18
ER -