EFFECTS OF POSTMORTEM DELAY ON HIGH-AFFINITY FORSKOLIN BINDING-SITES AND ADENYLATE-CYCLASE ACTIVITY IN RAT AND HUMAN STRIATUM AND CEREBRAL-CORTEX

High affinity [H-3]forskolin binding was measured using quantitative a utoradiography in the striatum and frontal cortex of rat and human bra in. Forskolin binding in rat striatum (310.8+/-26.0 pmol/g mean+/-S.E. M.) was approximately 4 times that in the frontal cortex (75.5+/-8.4 p mol/g), whereas in post-mortem human brain each region exhibited simil ar levels of forskolin binding (striatum 51.3+/-1.2 and cortex 53.2+/- 2.1 pmol/g). Basal adenylate cyclase activity was assayed in membranes prepared from striatum and frontal cortex of rat and human; enzyme ac tivity in the rat striatum was approximately 2-fold that in rat fronta l cortex whereas enzyme activity in the human striatum was similar to that in the human frontal cortex. To investigate the effect of the int erval between death and freezing of the brain, rats were killed by dec apitation, then maintained at 37 degrees C for up to 4 hours before fr eezing and subsequent assay of forskolin binding and adenylate cyclase activity. Striatal forskolin binding declined markedly post-mortem su ch that 4 h post-mortem it was only 13% of the level in control animal s while levels of cortical forskolin binding declined minimally during the immediate post-mortem period. Striatal and cortical adenylate cyc lase activity (basal) was minimally influenced by post-mortem delay al though in both regions there was a rapid loss of the ability of fluoro aluminate to stimulate adenylate cyclase. The data suggest that the st riatum contains a population of high affinity forskolin binding sites which is extremely sensitive to post-mortem delay. These forskolin bin ding sites may exist as an alternative or additional population to the more post-mortem delay-insensitive type observed in frontal cortex. I nterpretation of studies of membrane transduction mechanisms in human pathologies and after cerebral ischaemia, as reflected by forskolin bi nding, must be approached bearing these findings in mind.