Guanine nucleotide regulatory proteins in the spontaneously hypertensive rat.
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.
Clark
C J
CJ
MRC Blood Pressure Unit, Western Infirmary, Glasgow, Scotland, UK.
Milligan
G
G
McLellan
A R
AR
Connell
J M
JM
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
D008024:Ligands; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases