Cyclic AMP accumulation in rabbit aorta smooth muscle cells altered in the presence of hyperlipidemic serum.
We investigated the effect of hyperlipidemic serum on cAMP accumulation in cultured smooth muscle cells from the rabbit aorta. The cells were grown to confluence, then cultured for 24 h in hyperlipidemic medium (total cholesterol: 2.2 mmol/l). cAMP accumulation was enhanced in response to isoproterenol 10(-6) M, as compared to control cells, and this enhancement was still detectable in the presence of IBMX 10(-3) M, a potent inhibitor of phosphodiesterase. Application of propranolol 10(-4) M at 5 min after isoproterenol showed a similar time course for cAMP disappearance. The phosphodiesterase activity in the 40 000 g supernatant of the Triton X-100 solubilized homogenates of the cells in hyperlipidemic medium remained unchanged. Beta-receptor assays showed an increased Bmax with a similar Kd, and such may contribute, at least in part, to the increased adenylate cyclase activity. An extended incubation in the presence of hyperlipidemic medium attenuated the cAMP accumulation, possibly due to excessive increases in the total cholesterol content.
Kishi
Y
Y
Nishiyama
K
K
Numano
F
F
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000225:Adenine / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D006949:Hyperlipidemias / Q000097:blood / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D002784:Cholesterol; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000225:Adenine; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine