The effects of tetramethylpyrazine on the human platelet alpha 2 adrenergic receptor adenylate cyclase system.
The binding properties of tetramethylpyrazine (TMPZ), a commonly used cardiovascular drug in China, to alpha 2 adrenergic receptors in human platelets were investigated. Increasing concentrations of TMPZ inhibited [3H]-yohimbine binding in intact platelets. The displacement curve was parallel to those of clonidine and yohimbine, with a Ki of 7.7 X 10(-5) M and an IC50 of 1.2 X 10(-4) M. In platelet membranes, increasing concentrations of TMPZ shifted the saturation binding curves of [3H]-yohimbine to the right and caused the dissociation constant (KD) to increase gradually. Higher concentrations of [3H]-yohimbine overcame the inhibition of TMPZ. Furthermore, in platelet cyclic AMP generation experiments, higher concentrations of TMPZ (10(-4)M-10(-6)M) inhibited the cyclic AMP increases induced by 10(-5) M PGE1. However, in the presence of an alpha 2 adrenergic receptor agonist (L-epinephrine), TMPZ blocked the inhibitory effect of L-epinephrine on cyclic AMP increases induced by PGE1. These properties suggested that TMPZ is an alpha 2 adrenergic receptor partial agonist. These effects may provide potential mechanisms for the cardiovascular actions of TMPZ.
Hui
K K
KK
Department of Medicine, UCLA School of Medicine 90024.
Yu
J L
JL
Tse
E
E
Borst
S
S
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D011719:Pyrazines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D002121:Calcium Channel Blockers; D011719:Pyrazines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000262:Adenylyl Cyclases; C017953:tetramethylpyrazine