Maintenance of adenosine A1receptor 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 A1receptors 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 A1receptor of the turtle brain. The rat brain had a 10-fold greater density of A1 receptors compared with the turtle [rat cortex receptor density (Bmax) = 1,400 ± 134.6 fmol/mg protein, turtle forebrain Bmax = 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 Bmax 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 Bmax 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 GABAA 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 A1receptor 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.