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 A₁ receptors using cyclopentyl-1,3-dipropylxanthine,8-[dipropyl-2,3-³H(N)] ([³H]DPCPX) saturation binding analyses and determined the effects of prolonged anoxia (6, 12, and 24 h) on the adenosine A₁ receptor of the turtle brain. The rat brain had a 10-fold greater density of A₁ 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 A₁ receptor function is rapidly compromised in anoxia, in the turtle forebrain no significant changes in the A₁ 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 A₁ receptor function and an increased A₁ sensitivity in the hindbrain may be important factors for maintaining the adenosine-mediated downregulation of energy demand during long-term anoxia.

cyclopentyl-1,3-dipropylxanthine,8-[dipropyl-2,3-³H(N)]; ischemia