Desensitization of the stimulatory A2 adenosine receptor-adenylate cyclase system in vascular smooth muscle cells from rat aorta.
We have previously shown that adenylate cyclase present in rat aorta vascular smooth muscle cells can be stimulated by adenosine, its analogs and other agonists. In the present studies, we have examined the effect of preexposure of aorta vascular smooth muscle cells to N-ethylcarboxamide adenosine (NECA) on adenylate cyclase activity stimulated by NECA and other agonists. The vascular smooth muscle cells, when exposed to NECA, resulted in a concentration- and time-dependent loss of NECA-stimulated adenylate cyclase activity. NECA stimulated adenylate cyclase activity by about 120% in control cells, which was decreased to 20% in cells pretreated with 50 microM NECA for 30 min at 37 degrees C. However, GTP-, isoproterenol-, and forskolin-sensitive adenylate cyclase activities were not affected by such treatment, suggesting that NECA treatment of the cells resulted in homologous desensitization. Similarly, the exposure of the cells to isoproterenol resulted in the desensitization of isoproterenol-stimulated adenylate cyclase activity without affecting the NECA-stimulated adenylate cyclase activity. Furthermore, when NECA-treated cells were washed free of agonist, the desensitized state was reversed and the cells regained about 75% responsiveness to NECA stimulation of adenylate cyclase.
Anand-Srivastava
M B
MB
Clinical Research Institute of Montreal, Quebec, Canada.
Cantin
M
M
Ballak
M
M
Picard
S
S
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*
D011983:Receptors, Purinergic; D019830:Adenosine-5'-(N-ethylcarboxamide); D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000241:Adenosine