Cell Biology International (1999) 23, 519522 (Printed in Great Britain)
MODULATION OF A2AADENOSINE RECEPTOR(S) BY K+ATPCHANNELS IN BOVINE BRAIN STRIATAL MEMBRANES
Hammed A. Olanrewajuf1, Ravi B. Maralaf2 and S.Jamal Mustafa
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC, 27858, U.S.A.
The modulation of adenosine receptor with K+ATPchannel blocker, glibenclamide, was investigated using the radiolabeled A2A-receptor selective agonist [3H]CGS 21680. Radioligand binding studies in bovine brain striatal membranes (BBM) indicated that unlabeled CGS 21680 displaced the bound [3H]CGS 21680 in a concentration-dependent manner with a maximum displacement being approximately 65% at 10−4. In the presence of 10−5 glibenclamide, unlabeled CGS 21680 increased the displacement of bound [3H]CGS 21860 by approximately 28% at 10−4. [3H]CGS 21680 bound to BBM in a saturable manner to a single binding site (Kd=10.6±1.71n ; Bmax=221.4±6.43fmol/mg of protein). In contrast, [3H]CGS 21680 showed saturable binding to two sites in the presence of 10−5 glibenclamide; (Kd=1.3± 0.22n ; Bmax=74.3±2.14fmol/mg protein; and Kd=8.9±0.64n ; Bmax=243.2±5.71fmol/mg protein), indicating modulation of adenosine A2Areceptors by glibenclamide. These studies suggest that the K+ATPchannel blocker, glibenclamide, modulated the adenosine A2Areceptor in such a manner that [3H]CGS 21680 alone recognizes a single affinity adenosine receptor, but that in the presence of glibenclamide it binds to two sites. These studies provide further insight into the interactions between K+ATPchannels and adenosine receptors.
Key words: K+ATPchannels, A2Aadenosine receptors, bovine striatal membranes, glibenclamide.
f1To whom correspondence should be addressed: Hammed A. Olanrewaju, Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, U.S.A.
f2Present address: Pfizer Central Research, Eastern Point Road, Groton, CT 06340, U.S.A.
Received 11 November 1998; accepted 29 March 1999