Guanine nucleotide regulatory protein alterations in young Milan hypertensive strain rats |
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Authors: | Catherin J. Clark Graeme Milligan John M.C. Connell |
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Affiliation: | 1. MRC Blood Pressure Unit, Western Infirmary, Glascow G11 6NT, UK;2. Molecular Pharmacology Group, Department of Biochemistry, University of Glasgow, Gr12 8QQ, UK |
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Abstract: | Vascular smooth muscle cell membranes from prehypertensive rats of the Milan hypertensive strain (MHS) were used to examine adenylyl cyclase activity and its regulation by guanine nucleotide regulatory proteins (G-proteins). Basal adenylyl cyclase activity was similar in MHS and Milan normontensive strain (MNS) membranes. Forsokolin (10?4 M) produced a significantly greater stimulatory response in MHS membranes, but this was not observed with NaF (10?2 M). Isoporterenol (10?4 M) caused a significantly decreased stimulation of adenylyl cyclase activity in MHS membranes, while prostaglandin E1 (10?5 M) produced similar responses in the two strains. Gi function and GTP responses, as observed by biphasic effects of GTP on isoproterenol-stimulated membranes, were similar in both strains. The levels of Gi2α and Gqα/G11α were similar in the two strains, while the levels of Gsα (44 and 42 kDa forms) and the β-subunit were significantly reduced by ~20% in MHS membranes. The α-subunit of Gi3 was dramatically reduced by ~80% in MHS membranes. The affinities of β-adrenergic receptors for the antagonist, cyanophindolol, were similar in the two strains; however, the number of β-adrenoceptors was substantially reduced in MHS membranes. These findings may be of relevance to altered vascular reactivity and transmembrane ion distribution observed in the MHS. |
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Keywords: | Vascular smooth muscle Adenylyl cyclase Guanine nucleotide regulatory protein Hypertensionl Membrane (Milan rat) ACA adenylyl cyclase activity maximal specific binding per unit of membrane protein cpm counts per minute CYP cyanophindolol DG diacylglycerol G-protein guanine nucleotide regulatory protein HRP horseradish peroxidase 5-HT 5-hydroxytryptamine inositol 1,4,5,-trisphosphate equilbrium dissociation constant MHS Milan hypertensive strain MNS Milan normotensive strain SBP systolic blood pressure SDS-PAGE sodium dodcyl sulphate polyacrylamide gel electrophoresis S.E.M. standared error of the mean SHR spontaneously hypertensive rat VSMC vascular smooth muscle cells |
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