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Abnormality of adenylate cyclase regulation in human platelet membranes in renal insufficiency
Author(s) -
JACOBSSON B.,
RANSNÄS L.,
NYBERG G.,
BERGH C.H.,
MAGNUSSON Y.,
HJALMARSON Å.
Publication year - 1985
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1985.tb00148.x
Subject(s) - cyclase , adenylate kinase , endocrinology , medicine , yohimbine , platelet , receptor , chemistry , adrenergic receptor , beta 3 adrenergic receptor , biology , antagonist
. Adenylate cyclase in human platelets is under dual control of prostaglandins (PGI 2 and PGE 1 ) and catecholamines. The adenylate cyclase complex in membranes of platelets from ten patients with uraemia was investigated. The activation of the platelet cyclase by PGEi is increased in the uraemic state, V max 4436 ± 607 pmol cAMP mg ‐1 15 min ‐1 . In the normal state V max is 2098 ± 309 pmol cAMP mg ‐1 15 min ‐1 . The alpha 2 ‐adrenergic receptor was assayed with 3 H‐yohimbine binding. The density of receptors was equal in the uraemic (175 fmol mg ‐1 membrane protein) and the normal (170 fmol mg ‐1 membrane protein) states. Norepinephrine/ 3 H‐yohimbine competition binding revealed that catecholamines were bound with normal affinity in platelets in uraemia. Yet the inhibition of adenylate cyclase through the alpha2–adrenergic receptor was diminished since V max values of adenylate cyclase with PGE 1 and PGE 2 + norepineprine did not significantly differ. In the normal state, norepinephrine significantly ( P < 0·05) inhibited the PGE 1 stimulated cyclase. It is concluded that platelet adenylate cyclase in the uraemia has an increased capacity for activation which is the result of both a sensitized stimulatory mechanism (prostaglandin mediated) and a deficient inhibitory mechanism (catecholamine mediated). It is suggested that a defect exists in the inhibitory nucleotide binding protein (N 1 ) which is the coupling unit between the adenylate cyclase catalytic subunit (C).