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Radioimmunoassay for Cyclic Nucleotides

III. EFFECT OF ISCHEMIA, CHANGES DURING DEVELOPMENT AND REGIONAL DISTRIBUTION OF ADENOSINE 3',5'-MONOPHOSPHATE AND GUANOSINE 3',5'-MONOPHOSPHATE IN MOUSE BRAIN

From the ¹ From the Metabolism Division, Department of Medicine and Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110

The levels of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) were measured in eight regions of mouse central nervous system (CNS), utilizing a recently developed radioimmunological assay. The effect of postnatal development and of ischemia on regional CNS cAMP and cGMP levels were studied also. Levels of cAMP were found to vary from 0.6 µmole per kg, wet weight, in spinal cord to 2.3 µmoles per kg, wet weight, in striatum. cGMP levels in most of the CNS were much lower, 33 to 69 nmoles per kg, wet weight, except in cerebellum, where the concentration of cGMP was 630 nmoles per kg, wet weight, 10 to 20 times that in any other region. Ischemia produced a 4-fold increase in cerebral cortical and cerebellar cAMP levels within 60 s, but with continued ischemia cAMP levels subsequently decreased. Levels of cGMP did not change during the initial 60 s of ischemia, and then decreased 60% in cerebral cortex and 80% in cerebellum. During the 1st week after birth, no changes in the levels of the two cyclic nucleotides in either forebrain or hindbrain were observed. Between 7 days and 21 days after birth, cAMP levels in forebrain, brain stem, and cerebellum increased 2-fold. The changes in cGMP levels between 7 days and adulthood were quite unlike those of cAMP. There was no change in forebrain cGMP, brain stem cGMP increased 2-fold, and in cerebellum cGMP rose dramatically, to a level 13 times that at 7 days.

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