Maintenance of adenosine A1 receptor function during long-term anoxia in the turtle brain

It has been established that adenosine has a critical role in the extraordinary ability of the turtle brain to survive anoxia. To further investigate this phenomenon we compared rat and turtle brain adenosine A(1) receptors using cyclopentyl-1,3-dipropyl-xanthine,8-[ dipropyl-2,3-H-3(N)] ([H-3]DPCPX) saturation binding analyses and determined the effects of prolonged anoxia (6, 12, and 24 h) on the adenosine A(1) receptor of the turtle brain. The rat brain had a 10-fold greater density of A(1) receptors compared with the turtle [rat cortex receptor density (B-max) = 1,400 +/- 134.6 fmol/mg protein, turtle forebrain B-max = 103.2 +/- 4.60 fmol/mg protein] and a higher affinity [dissociation constant (K-d) rat cortex = 0.328 +/- 0.035 nM, K-d turtle forebrain = 1.16 +/- 0.06 nM]. However, the turtle K-d is within the reported mammalian range, and the B-max is similar to that reported for other poikilotherms. Unlike the mammal, in which A(1) receptor function is rapidly compromised in anoxia, in the turtle forebrain no significant changes in the A(1) receptor population were seen during 24-h anoxia. However, in the hindbrain, whereas the B-max remained unchanged, the K-d significantly decreased from 2.1 to 0.5 nM after 6 h anoxia and this higher affinity was maintained at 12- and 24-h anoxia. These findings indicate that, unlike the GABA(A) receptor, the protective effectiveness of adenosine in the anoxic turtle brain is not related to an enhanced receptor number. Protection from a hypoxia-induced compromise in A(1) receptor function and an increased A(1) sensitivity in the hindbrain may be important factors for maintaining the adenosine-mediated downregulation of energy demand during long-term anoxia.