Regional localization ny light microscopic autoradiography of receptors in mouse brain for phorbol ester tumor promoters

Nagle, Denise S.; Blumberg, Peter M.

doi:10.1016/0304-3835(83)90115-5

Cited by 28 publications

(12 citation statements)

References 11 publications

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“…Hence, our experiment is a semiquantitative autoradiographic study. The distribution of 3H-PDBu binding sites in the adult rat brain was similar to those previously observed by in vitro autoradiography (Nagle and Blumberg, 1983;Worley et al, 1986). Our results revealed that the developmental pattern of 3H-PDBu binding sites showed considerable variation in different brain regions.…”

Section: Discussionsupporting

confidence: 86%

“…5b, c). As observed in previous reports (Nagle and Blumberg, 1983;Worley et al, 1986), a very high density was found in the molecular layer of the cerebellum, while the adjacent granular layer had few binding sites in the adult rat brain. 3H-PDBu binding sites in the molecular layer reached an adult level at 28 days of postnatal age.…”

Section: Resultssupporting

confidence: 74%

“…Protein kinase C exists in a variety of tissues and is most concentrated in the central nervous system Kikkawa et al, 1982;Minakuchi et al, 1981). The 42 R. Miyoshi and S. Kito morphological distribution of protein kinase C in the brain has been elucidated with the use of both immunohistochemical analysis with antisera against the enzyme (Girard et al, 1985;Hidaka et al, 1988;Kitano et al, 1987;Wood et al, 1986) and in vitro autoradiography with a radiolabelled phorbol ester, 3H-phorbol 12,13-dibutyrate (3H-PDBu) (Nagle and Blumberg, 1983;Worley et al, 1986). Results obtained from both techniques revealed an uneven distribution of protein kinase C, that is, high densities of the enzyme were present in the olfactory tubercle, cerebral cortex, amygdaloid complex, striatum, hippocampus, cerebellar cortex and so on.…”

Section: Introductionmentioning

confidence: 99%

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Ontogeny of phorbol ester receptors in rat brain studied by in vitro autoradiography

Miyoshi

Kito

1990

J. Neural Transmission

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The ontogeny of phorbol ester receptors, which have been considered to correspond to protein kinase C, in the rat brain was studied through in vitro autoradiography with 3H-phorbol 12,13-dibutyrate (3H-PDBu). The distribution of 3H-PDBu binding sites in the adult rat brain was similar to the previous reports by other researchers. The developmental pattern of 3H-PDBu binding sites varied with brain region. 3H-PDBu binding sites in the amygdala, thalamus, stratum pyramidale of CA 1 of the hippocampus, dentate gyrus, superior colliculus, substantia nigra, interpeduncular nucleus and cerebellar molecular layer were postnatally increased to adult levels and after that they remained constant. On the other hand, in the stratum oriens and stratum radiatum of CA 1 of the hippocampus, and in the lateral and medial geniculate bodies, 3H-PDBu binding sites reached peaks at 21 or 28 days of postnatal age and after that they declined to adult levels. The cerebellar granular layer showed a low level of 3H-PDBu binding sites throughout all the ontogenetic stages. A distinct ontogenetic pattern of phorbol ester receptors in various regions of the brain may reflect a role of protein kinase C in the neural development of each discrete area.

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Section: Discussionsupporting

confidence: 86%

Section: Resultssupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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Ontogeny of phorbol ester receptors in rat brain studied by in vitro autoradiography

Miyoshi

Kito

1990

J. Neural Transmission

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“…1). The density of phorbol ester receptors varied widely among grey matter areas, as reported by Nagle and Blumberg for the mouse brain (16). The hippocampus, cerebral cortex, and striatum were densely labeled, while large areas of the hypothalamus had low levels of activity.…”

Section: Resultsmentioning

confidence: 78%

“…Autoradiography was performed according to the methods of Palacios et al (15) and of Nagle and Blumberg (16). Rats were perfused via the left ventricle with phosphate-buffered saline followed by 0.32 M sucrose.…”

Section: Methodsmentioning

confidence: 99%

Protein kinase C regulates ionic conductance in hippocampal pyramidal neurons: electrophysiological effects of phorbol esters.

Baraban¹,

Snyder²,

Alger³

1985

Proc. Natl. Acad. Sci. U.S.A.

304

149

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The vertebrate central nervous system contains very high concentrations of protein kinase C, a calciumand phospholipid-stimulated phosphorylating enzyme. Phorbol esters, compounds with inflammatory and tumor-promoting properties, bind to and activate this enzyme. To clarify the role of protein kinase C in neuronal function, we have localized phorbol ester receptors in the rat hippocampus by autoradiography and examined the electrophysiological effects of phorbol esters on hippocampal pyramidal neurons in vitro. Phorbol esters blocked a calcium-dependent potassium conductance. In addition, phorbol esters blocked the late hyperpolarization elicited by synaptic stimulation even though other synaptic potentials were not affected. The potencies of several phorbol esters in exerting these actions paralleled their affinities for protein kinase C, suggesting that protein kinase C regulates membrane ionic conductance.Protein kinase C, a phosphorylating enzyme stimulated by calcium and phospholipid, occurs ubiquitously in the body but is most concentrated in the brain (1-4). In peripheral tissues, protein kinase C may mediate cellular responses to membrane receptor stimulation; however, its role in the central nervous system is largely unknown (5-10). Phorbol esters, lipophilic compounds with inflammatory and tumorpromoting properties, may facilitate studies of protein kinase C, since they directly stimulate this enzyme (4, 11-13). Phorbol esters have been used as probes to demonstrate a role of protein kinase C in regulating effects of neurotransmitters on smooth muscle (14). To clarify the role of protein kinase C in neuronal function, we have now localized phorbol ester receptors in the rat hippocampus by autoradiography and studied the effects of phorbol esters on hippocampal pyramidal neurons by using intracellular recording techniques in the slice preparation in vitro. Phorbol esters potently affect neuronal electrophysiological properties, suggesting that protein kinase C regulates membrane ionic conductance. MATERIALS AND METHODSAutoradiography. Autoradiography was performed according to the methods of Palacios et al. (15) and of Nagle and Blumberg (16). Rats were perfused via the left ventricle with phosphate-buffered saline followed by 0.32 M sucrose. Eight-micrometer-thick brain sections were cut on a cryostat and thaw-mounted onto microscope slides coated with chrome alum/gelatin. Slide-mounted tissue sections were incubated at room temperature with 2-3 nM 3H-labeled phorbol 12,13-dibutyrate (PBt2) (New England Nuclear) for 45 min in buffer containing 50 mM Tris HCl at pH 7.7 and 100 mM NaCl. To determine nonspecific binding, adjacent sections were incubated in the same medium with the addition of 1 uM unlabeled PBt2. After incubation, tissue sections were washed for 4 min at 40C, dipped in deionized water, and dried rapidly under a stream of cold dry air. After this labeling procedure, the slide-mounted tissue sections were juxtaposed to a tritium-sensitive film (Ultrafilm, LKB, Bromma, Sweden) in a s...

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The Family of Protein Kinase C for Signal Transduction

Nishizuka¹

1989

JAMA

320

151

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Protein kinase C, an enzyme that is activated by diacylglycerol resulting from the receptor-mediated hydrolysis of inositol phospholipids, relays information of a variety of extracellular signals across the cell membrane to regulate many intracellular processes. Since this enzyme also serves as a major receptor for phorbol esters, a class of tumor promoters, it has attracted great attention from biologists interested in the mechanism of signal transduction and carcinogenesis. Recent analysis has revealed that protein kinase C is a large family of proteins, with the multiple subspecies that possess subtle individual enzymological characteristics. Biochemical and immunohistochemical studies indicate that the protein kinase C subspecies may be differently distributed in particular cell types and with limited intracellular locations. Presumably, each member of the family plays discrete roles in the processing of various physiological and pathological responses to external signals, such as in the modulation of membrane functions and the activation of gene transcription.

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Regional localization ny light microscopic autoradiography of receptors in mouse brain for phorbol ester tumor promoters

Cited by 28 publications

References 11 publications

Ontogeny of phorbol ester receptors in rat brain studied by in vitro autoradiography

Ontogeny of phorbol ester receptors in rat brain studied by in vitro autoradiography

Protein kinase C regulates ionic conductance in hippocampal pyramidal neurons: electrophysiological effects of phorbol esters.

The Family of Protein Kinase C for Signal Transduction

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