Decrease in A1 adenosine receptors in adipocytes from spontaneously hypertensive rats.
We have investigated whether the insulin resistance reported to occur in hypertension is due to decreased insulin receptors or to adenosine receptors in adipocyte membranes. Membranes were isolated from adipocytes from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKy) rats and assayed for insulin receptors and A1 adenosine receptors. The two groups of membranes bound 125I-insulin equally, but in contrast the SHR membranes bound approximately 25% less 125I-HPIA ([(-)-N6-p-hydroxyphenylisopropyl adenosine], an A1 adenosine receptor agonist) than the WKy (P less than .005). Scatchard analysis demonstrated that this was due to a lower number of receptors in the SHR. The affinity of the receptor for HPIA was approximately 0.7 nmol/L in both groups. 5'-Nucleotidase activity was approximately 40% higher in membranes from SHR than WKy (P less than .001), indicating that adipocytes from SHR have a higher capacity for adenosine production. This may cause increased adenosine concentrations in the SHR adipose tissue, leading to adenosine receptor down-regulation. Since we have previously demonstrated that adenosine receptor down-regulation can lead to insulin resistance, these findings may partly account for the insulin resistance of hypertension.
Green
A
A
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Johnson
J L
JL
DiPette
D J
DJ
D015720:5'-Nucleotidase / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure; D002462:Cell Membrane / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D010660:Phenylisopropyladenosine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011972:Receptor, Insulin / Q000378:metabolism; D011983:Receptors, Purinergic / Q000378:metabolism*
D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; C036265:N-(4-hydroxyphenyl)-1-isopropyladenosine; D011972:Receptor, Insulin; D015720:5'-Nucleotidase