[Anomalies of the adenylate cyclase system in platelets of the SHR rat].
The hormone-sensitive adenylate cyclase system of plasma membrane is composed of at least three types of proteins: hormone receptors, activatory (Gs) and inhibitory (Gi) guanine nucleotide-regulatory proteins and the catalytic unit (C). Abnormal hormonal regulations of platelet adenylate cyclase in both humans and experimental animals have been reported to occur in hypertension. However, little is known about the mechanisms for these alterations. The aim of the present study was to compare the activity of C and the inhibitory capacity of Gi in platelet membranes from spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). Adenylate cyclase activity of 40,000 g membranes was assessed at pH 7.5 with 0.1 mM (alpha-32P) ATP and an appropriate bivalent cation (Mn2+ or Mg2+). Under incubation conditions that uncoupled C from Gs and Gi (25 mM MnCL2, 100 microM forskolin), a significantly lower adenylate cyclase activity was measured in membranes from SHR rats (2.07 +/- 0.12 vs 2.36 +/- 0.1 nmol cAMP/mn/mg of protein, p less than 0.05). This difference between the two strains was also observed in platelet homogenates. In a second kind of experiments, membranes were incubated with 2.1 mM MgCl2 instead of MnCl2. In both strains of rats, low concentrations of Gpp (NH)p (10 to 300 nM) inhibited adenylate cyclase activity when stimulated by 50 microM forskolin. However, the maximal extent of inhibition was significantly reduced in hypertensive rats (49.7 +/- 2.4 vs 60.5 +/- 2.3 p. 100, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Coquil
J F
JF
INSERM U 7, hôpital Necker, Paris.
Brunelle
G
G
Meyer
P
P
D000262:Adenylyl Cyclases / Q000097:blood*; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D019204:GTP-Binding Proteins / Q000097:blood; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D008345:Manganese; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium
Anomalies du système adénylate cyclasique des plaquettes du rat SHR.