Abnormality of adenylate cyclase regulation in human platelet membranes in renal insufficiency.

Jacobsson, BGothenburg University,Göteborgs universitet,Medicinska institutionen,Department medicine (author)

Adenylate cyclase in human platelets is under dual control of prostaglandins (PGI2 and PGE1) and catecholamines. The adenylate cyclase complex in membranes of platelets from ten patients with uraemia was investigated. The activation of the platelet cyclase by PGE1 is increased in the uraemic state, Vmax 4436 +/- 607 pmol cAMP mg-1 15 min-1. In the normal state Vmax is 2098 +/- 309 pmol cAMP mg-1 15 min-1. The alpha 2-adrenergic receptor was assayed with 3H-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/3H-yohimbine competition binding revealed that catecholamines were bound with normal affinity in platelets in uraemia. Yet the inhibition of adenylate cyclase through the alpha 2-adrenergic receptor was diminished since Vmax values of adenylate cyclase with PGE1 and PGE2 + norepinephrine did not significantly differ. In the normal state, norepinephrine significantly (P less than 0.05) inhibited the PGE1 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 (NI) which is the coupling unit between the adenylate cyclase catalytic subunit (C).

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Dermatologi och venereologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Dermatology and Venereal Diseases hsv//eng
Adenylate Cyclase
blood
Adult
Alprostadil
Binding
Competitive
Blood Platelets
enzymology
Cell Membrane
enzymology
Enzyme Activation
drug effects
Female
Glomerulonephritis
complications
Humans
Male
Middle Aged
Norepinephrine
metabolism
pharmacology
Prostaglandins E
pharmacology
Receptors
Adrenergic
alpha
metabolism
Uremia
enzymology
etiology
Yohimbine
metabolism

Ransnäs, LGothenburg University,Göteborgs universitet,Medicinska institutionen,Department medicine (author)
Nyberg, GGothenburg University,Göteborgs universitet,Medicinska institutionen,Department medicine (author)
Bergh, C HGothenburg University,Göteborgs universitet,Medicinska institutionen,Department medicine (author)
Magnusson, Yvonne,1957Gothenburg University,Göteborgs universitet,Medicinska institutionen,Department medicine(Swepub:gu)xmagyv (author)
Hjalmarson, Agneta,1943Gothenburg University,Göteborgs universitet,Medicinska institutionen,Department medicine(Swepub:gu)xhjaag (author)
Göteborgs universitetMedicinska institutionen (creator_code:org_t)

By the author/editor: Jacobsson, B; Ransnäs, L; Nyberg, G; Bergh, C H; Magnusson, Yvonn ...; Hjalmarson, Agne ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Dermatology and ...

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