Species differences in alpha 2-adrenergic regulation of platelet adenylate cyclase.
Species differences in the ability of alpha 2-adrenergic receptors to down-regulate platelet adenylate cyclase activity were compared in platelet membranes derived from man, rabbit and rat. In all three, prostaglandin E1 and forskolin caused massive stimulation of enzyme activity, without species selectivity. However, alpha 2-receptor actions revealed marked species dissimilarities: clonidine caused 20-30% inhibition of human and rabbit basal adenylate cyclase, prostaglandin E1-stimulated activity and forskolin-stimulated activity, but failed to inhibit activity in the rat preparation. [3H]Rauwolscine binding indicated that rat platelets are deficient in alpha 2-receptor sites. Because rat brain is not deficient in alpha 2-receptors, these results indicate that care should be exercised in the use of platelet systems in animal models of psychotropic drug administration. Furthermore, although clonidine was effective in both man and rabbit, differences in sensitivity to alpha 2-receptor stimulation were also apparent; clonidine was more effective in inhibiting the response to prostaglandin E1 in man, but inhibition of the forskolin response was more prominent in the rabbit. Accordingly, multiple modes of stimulation need to be examined in delineating the inhibitory control of adenylate cyclase by alpha 2-receptors.
Slotkin
T A
TA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
McCook
E C
EC
Nemeroff
C B
CB
Seidler
F J
FJ
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000097:blood*; D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology*; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D011817:Rabbits; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013045:Species Specificity; D013223:Statistics as Topic; D015016:Yohimbine / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D015016:Yohimbine; D000262:Adenylyl Cyclases; D000527:Alprostadil; D003000:Clonidine