Epinephrine stimulates inositol phospholipid metabolism by activating alpha-2 adrenergic receptors in human platelets.
The metabolism of inositol phospholipids in response to epinephrine was investigated in intact human platelets. In platelets prelabelled with [3H]-myo-inositol in Ca2+-free HEPES buffer containing 10 mM LiCl, epinephrine caused an accumulation of inositol-1-phosphate in a concentration-dependent manner. The EC50 value for epinephrine was 5 microM. Yohimbine (1 microM), a selective alpha-2 adrenergic receptor antagonist, inhibited 88% of the epinephrine (10 microM) response, whereas prazosin (1 microM), a selective alpha-1 adrenergic receptor antagonist, failed to inhibit the response. Yohimbine inhibited the epinephrine (10 microM) response in a concentration-dependent manner. The inhibition constant (Ki) value for yohimbine was 60.3 nM. These data indicate that epinephrine stimulates phosphoinositide (PI) turnover by activating adrenergic receptors of the alpha-2 type in human platelets. In addition, this PI response elicited by epinephrine was found to be inhibited in a concentration-dependent manner by treatment of platelets with dibutyryl cyclic AMP and 8-bromo-cyclic GMP which are known as potent inhibitors for platelet activation, and may therefore be a useful biochemical index for the study of the function of human alpha-2 adrenergic receptors.
Mori
H
H
Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
Mikuni
M
M
Koyama
T
T
Yamashita
I
I
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D007294:Inositol / Q000097:blood; D007295:Inositol Phosphates / Q000097:blood*; D008803:Mianserin / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013403:Sugar Phosphates / Q000097:blood*; D015016:Yohimbine / Q000494:pharmacology
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D013403:Sugar Phosphates; C002647:inositol 1-phosphate; D008803:Mianserin; D015016:Yohimbine; C016276:8-bromocyclic GMP; D007294:Inositol; D003994:Bucladesine; D006152:Cyclic GMP; D011224:Prazosin; D004837:Epinephrine