title: Guanine nucleotide regulatory protein alterations in young Milan hypertensive strain rats.
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 normotensive strain (MNS) membranes. Forskolin (10(-4) M) produced a significantly greater stimulatory response in MHS membranes, but this was not observed with NaF (10(-2) M). Isoproterenol (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 Gi2 alpha and Gq alpha/G11 alpha were similar in the two strains, while the levels of Gs alpha (44 and 42 kDa forms) and the beta-subunit were significantly reduced by approximately 20% in MHS membranes. The alpha-subunit of Gi3 was dramatically reduced by approximately 80% in MHS membranes. The affinities of beta-adrenergic receptors for the antagonist, cyanopindolol, were similar in the two strains; however, the number of beta-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.
authors.affiliation: MRC Blood Pressure Unit, Western Infirmary, Glasgow, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Clark
authors.forename: G
authors.initials: G
authors.lastname: Milligan
authors.forename: J M
authors.initials: JM
authors.lastname: Connell
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007106:Immune Sera / Q000737:chemistry / Q000276:immunology; D007545:Isoproterenol / Q000494:pharmacology; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis; D015398:Signal Transduction
chemical_list: D007106:Immune Sera; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; C047975:cyanopindolol; D010869:Pindolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000527:Alprostadil; D007545:Isoproterenol