Summary
The effect of transient cerebral ischemia and intraventricular injection of kainic acid on adenylate cyclase and protein kinase C as labeled by [3H]forskolin ([3H]FOR) and [3H]phorboldibutyrate ester ([3H]PDBU) in several rat brain microregions was investigated in a quantitative autoradiographic study. Four days after transient four vessel occlusion a 80% loss of [3H]FOR and a 35% loss of [3H]PDBU binding could be measured in the CA1 stratum radiatum of operated Wistar rats as compared to control rats. Four days after intraventricular injection of kainic acid only a marginal loss of [3H]FOR and a 30% increase of [3H]PDBU binding was seen in the CA1 stratum radiatum while in the CA3 stratum lucidum and radiatum respectively a 30% loss of [3H]FOR and no significant change in [3H]PDBU binding was observed. As transient cerebral ischemia and intraventricular kainic acid injection are depleting the hippocampal CA1 region of CA1 pyramidal cells and axons of CA3 pyramidal cells respectively in rat brain, these findings strongly suggest that both adenylate cyclase and protein kinase C are localized in CA1 pyramidal cells of rat hippocampus.
Similar content being viewed by others
References
Daly JW, Padgett W, Creveling CR, Cantacuzene D, Kirk KL (1981) Cyclic-AMP generating systems. Regional differences in activation by adrenergic receptors in rat brain. J Neurosci 1(1): 49–59
Deckert J, Bisserbe J-C, Marangos PJ (1987) Quantitative [3H]dipyridamole autoradiography: evidence for adenosine transporter heterogeneity in guinea pig brain. Naunyn Schmiedebergs Arch Pharmacol 335: 660–666
Dunphy NG, Delclos KB, Blumberg PM (1980) Characterization of specific binding of [3H]Phorbol-12,13-dibutyrate and [3H]Phorbol-12-myristate-13-acetate to mouse brain. Cancer Res 40: 3635–3641
Dunwiddie TV, Fredholm BB (1985) Adenosine modulation of synaptic responses in rat hippocampus: possible role of inhibition or activation of adenylate cyclase. In: Cooper DMF, Seamon KB (eds) Advances in cyclic nucleotide protein phosphorylation research. Raven Press, New York, pp 259–272
Fredholm BB, Jonzon B, Lindgren E, Lindstrom K (1983) Adenosine receptor mediated increases and decreases in cyclic AMP in hippocampal slices treated with forskolin. Acta Physiol Scand 117: 461–463
Gehlert DR, Dawson TM, Yamamura HI, Wamsley JK (1985) Quantitative autoradiography of [3H]forskolin binding sites in the rat brain. Brain Res 361: 351–360
Goochee C, Rasband W, Sokoloff L (1980) Computerized densitometry and colour coding of [14C]deoxyglucose autoradiographs. Ann Neurol 7: 359–370
Johansen FF, Jorgensen MB, Diemer NH (1983) Resistance of hippocampal interneurons to 20 minutes of transient cerebral ischemia in the rat. Acta Neuropathol 61: 135–140
Johansen FF, Zimmer J, Diemer NH (1987) Loss of somatostatin neurons in dentate hilus after cerebral ischemia in the rat may induce delayed CA1 pyramidal cell loss. Acta Neuropathol 73: 110–114
Jorgensen MB, Diemer NH (1982) Selective neuron loss after cerebral ischemia: possible role of transmitter glutamate. Acta Neurol Scand 66: 536–546
Jorgensen MB, Johansen FF, Diemer NH (1987) Removal of the entorhinal cortex protects hippocampal CA1 neurons from ischemic damage. Acta Neuropathol 73: 189–194
Karbon EW, Shenolikar S, Enna SJ (1986) Phorbol esters enhance neurotransmitter-stimulated cyclic AMP production in rat brain slices. J Neurochem 47: 1566–1575
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239: 57–69
Labarca R, Janowsky A, Patel J, Paul SM (1984) Phorbol esters inhibit agonist-induced [3H]inositol-1-phosphate accumulation in rat hippocampal slices. Biochem Biophys Res Commun 123 (2): 703–709
Mochley-Rosen D, Basbaum AI, Koshland DE (1987) Distinct cellular and regional localization of immunoreactive protein kinase C in rat brain. Proc Natl Acad Sci USA 84: 4660–4664
Nadler JV, Perry BW, Cotman CW (1978) Preferential vulnerability of hippocampus to intraventricular kainic acid. In: McGeer EG, Olney JW, McGeer PL (eds) Kainic acid as a tool in neurobiology. Raven Press, New York, pp 219–237
Nichols RA, Haycock JW, Wang JKT, Greengard P (1987) Phorbol ester enhancement of neurotransmitter release from rat brain synaptosomes. J Neurochem 48: 615–621
Nicoletti F, Meek JL, Ladarola MJ, Chuang DM, Roth BL, Costa E (1986) Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus. J Neurochem 46: 40–46
Nordstedt C, Fredholm BB (1987) Phorbol-12, 13-dibutyrate enhances the cyclic AMP accumulation in rat hippocampal slices induced by adenosine analogues. NaunynSchmiedebergs Arch Pharmacol 335: 136–142
Onodera H, Araki T, Kogure K (1989) Protein kinase C activity in the rat hippocampus after forebrain ischemia: autoradiographic analysis by [3H]phorbol-12, 13-dibutyrate. Brain Res 481: 1–7
Parker PJ, Stabel T, Waterfield MD (1984) Purification to homogeneity of protein kinase C from bovine brain-identity with the phorbol ester receptor. EMBO J 3 (5): 953–959
Paxinos G, Watson C (1982) The rat brain in sterotaxic coordinates. Academic Press, New York
Seamon KB, Daly JW (1986) Forskolin: its biological and chemical properties. In: Greengard P, Robison GA (eds) Advances in cyclic nucleotide and protein phosphorylation research. Raven Press, New York, pp 1–150
Seamon KB, Vaillancourt R, Edwards M, Daly JW (1984) Binding of [3H]forskolin to rat brain membranes. Proc Natl Acad Sci USA 81: 5081–5085
Sibley DR, Benovic JL, Caron MG, Lefkowitz RJ (1987) Regulation of transmembrane signaling by receptor phosphorylation. Cell 48: 913–922
Worley PF, Baraban JM, Snyder SH (1986 a) Heterogenous localization of protein kinase C in rat brain: autoradiographic analysis of phorbolester receptor binding. J Neurosci 6 (1): 199–207
Worley PF, Baraban JM, de Souza EB, Snyder SH (1986 b) Mapping second messenger systems in the brain: differential localizations of adenylate cyclase and protein kinase C. Proc Natl Acad Sci USA 83: 4053–4057
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Deckert, J., Jorgensen, M.B. Post- and presynaptic lesions in the CA1 region of hippocampus: Effect on [3H]forskolin and [3H]phorboldibutyrate ester binding. J. Neural Transmission 83, 205–214 (1991). https://doi.org/10.1007/BF01253390
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01253390