Beta-adrenergic receptor activity of cerebral microvessels in experimental diabetes mellitus.
The effect of diabetes mellitus on beta-adrenergic receptor number (B(max)), receptor-cyclase coupling and adenylate cyclase (AC) activity was determined in cerebral microvessels isolated from control and streptozotocin induced diabetic rats after 5 weeks of induction of diabetes. Scatchard analysis of [125I]iodocyanopindolol (ICYP) binding indicated that the B(max) (fmol/mg) in diabetic rat cerebral microvessels (63.8 +/- 4.8) (mean +/- S.E.M.) was not significantly different from the B(max) in control rats (56.5 +/- 6.9). Isoproterenol competition of [125I]ICYP binding sites indicated that the percentage of beta-receptors expressing high affinity binding was 53.9 +/- 0.45% in control rats and 47.5 +/- 2.3% in diabetic rats. The total isoproterenol-stimulated AC activity (pmol cAMP/mg) in diabetic rats (76.7 +/- 6.1) was significantly lower than that in control rats (118.4 +/- 11.2) (P less than 0.01). However, the net isoproterenol-stimulated AC activity (i.e. total minus GTP-stimulated AC activity) was not altered in diabetes. The net sodium fluoride (NaF) stimulated AC activity in diabetic rats (109.5 +/- 11.4) was significantly lower than the control rats (154.3 +/- 16.3) (P less than 0.05). It is concluded that diabetes mellitus in rats is associated with reduced post receptor activation of adenylate cyclase in cerebral microvessels while the beta-adrenergic receptor density, affinity and receptor-cyclase coupling are not significantly altered.
Mooradian
A D
AD
St. Louis DVA Medical Center, MO.
Scarpace
P J
PJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008833:Microcirculation / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D016548:Prosencephalon / Q000098:blood supply*; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values; D012969:Sodium Fluoride / Q000494:pharmacology
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D012969:Sodium Fluoride; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol