title: Guanine nucleotide regulatory proteins in the spontaneously hypertensive rat.
abstract: We compared guanine nucleotide regulatory protein (G protein) levels and function in plasma membranes from resistance vessels (mesenteric arteries) isolated from spontaneously hypertensive (SHR) and normotensive Wistar rats. G protein function was deduced from studies of adenylate cyclase activity. Although the basal level of adenylate cyclase activity (+/- Mn2+ ions) was significantly greater in SHR membranes, addition of agents that function via the stimulatory G protein--i.e., NaF (10(-2) M), (-)-isoproterenol (10(-4) M), and prostaglandin E1 (10(-5) M)--resulted in a significantly lower stimulatory response in SHR membranes. Ligands that function via the inhibitory G protein--i.e., adrenaline (10(-5) M)/propranolol (10(-5) M) (this combination being equivalent to an alpha 2-receptor agonist), carbachol (10(-3) M), and serotonin (10(-5) M)--were responsible for only slight inhibitory responses in both SHR and Wistar rat membranes, which were not significantly different. Western blotting identified the presence of Gs, Gi2, and Gi3 alpha-subunits in rat vascular smooth muscle, but there were no differences in the levels of these G protein alpha-subunits found in SHR and Wistar rat plasma membranes. The levels of the beta-subunit in the two sets of membranes were also similar. In conclusion, there is a reduced response in adenylate cyclase activity to agents that function via the stimulatory G protein in SHR membranes. However, this is not a consequence of altered levels of the different G protein subunits.
authors.affiliation: MRC Blood Pressure Unit, Western Infirmary, Glasgow, Scotland, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Clark
authors.forename: G
authors.initials: G
authors.lastname: Milligan
authors.forename: A R
authors.initials: AR
authors.lastname: McLellan
authors.forename: J M
authors.initials: JM
authors.lastname: Connell
mesh_terms: D000262:Adenylyl Cyclases / Q000032:analysis; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015151:Immunoblotting; D008024:Ligands; D008638:Mesenteric Arteries / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D017208:Rats, Wistar; D013268:Stimulation, Chemical
chemical_list: D008024:Ligands; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases