Effects of post-mortem delay on high affinity forskolin binding sites and adenylate cyclase activity in rat and human striatum and cerebral cortex.
High affinity [3H]forskolin binding was measured using quantitative autoradiography in the striatum and frontal cortex of rat and human brain. 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 pmol/g), whereas in post-mortem human brain each region exhibited similar 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 activity in the rat striatum was approximately 2-fold that in rat frontal cortex whereas enzyme activity in the human striatum was similar to that in the human frontal cortex. To investigate the effect of the interval between death and freezing of the brain, rats were killed by decapitation, then maintained at 37 degrees C for up to 4 hours before freezing and subsequent assay of forskolin binding and adenylate cyclase activity. Striatal forskolin binding declined markedly post-mortem such that 4 h post-mortem it was only 13% of the level in control animals while levels of cortical forskolin binding declined minimally during the immediate post-mortem period. Striatal and cortical adenylate cyclase activity (basal) was minimally influenced by post-mortem delay although in both regions there was a rapid loss of the ability of fluoroaluminate to stimulate adenylate cyclase. The data suggest that the striatum contains a population of high affinity forskolin binding sites which is extremely sensitive to post-mortem delay.(ABSTRACT TRUNCATED AT 250 WORDS)
Ross
B
B
Wellcome Surgical Institute, University of Glasgow, UK.
Dawson
D
D
Dewar
D
D
Macrae
M
M
Knowler
J
J
McCulloch
J
J
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000378:metabolism; D002421:Caudate Nucleus / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism*; D005615:Freezing; D005625:Frontal Lobe / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008297:Male; D017072:Neostriatum / Q000201:enzymology / Q000378:metabolism*; D011180:Postmortem Changes; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*
D011956:Receptors, Cell Surface; C085974:forskolin receptor; D005576:Colforsin; D000262:Adenylyl Cyclases