Nicotinic and muscarinic agonists stimulate rapid protein kinase C translocation in PC12 cells

Messing, Robert O.; Stevens, Ann M.; Kiyasu, E.; Sneade, Alisa B.

doi:10.1523/jneurosci.09-02-00507.1989

Cited by 67 publications

(38 citation statements)

References 40 publications

(48 reference statements)

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“…Activation of the enzyme may involve association of the enzyme with the cell membrane (24) and subserve alterations in cellular responses in many systems (11,(25)(26)(27)(28). In this study, film autoradiography using (33,34). If the autoradiographic method were assaying both cytosolic PKC and mPKC, or artifactually translocating significant amounts of cytosolic PKC, it would not be able to detect carbacholstimulated PKC translocation.…”

Section: Discussionmentioning

confidence: 94%

Protein kinase C redistribution within CA3 stratum oriens during acquisition of nictitating membrane conditioning in the rabbit.

Scharenberg

Olds

Schreurs

et al. 1991

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

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This manuscript describes experiments designed to investigate protein kinase C redistribution occurring during acquisition of the rabbit nictitating membrane (NM) conditioned response (CR). The first experiment defined the acquisition phase of the NM response for our laboratory. A group of rabbits (n = 6) was given 2 days of paired NM training; a second group (n = 6) was given 2 days of unpaired NM training. The data document a variable level of responding on day 1 for rabbits given paired training (mean ± SEM, 21 ± 11% CRs) but show that on day 2 most rabbits reached the behavioral asymptote (five of six rabbits responding with >85% CRs). Rabbits responding at the behavioral asymptote were defined as having acquired the NM conditioned response. These data were interpreted to indicate that 1 day of training initiated processes necessary for behavioral acquisition (i.e., responding at the behavioral asymptote). A quantitative finm autoradiographic study of [3H]phorbol 12,13-dibutyrate binding was then used to determine the distribution of hippocampal protein kinase C in rabbits sacrificed after receiving either 1 day ofpaired stimuli (n = 10), 1 day of unpaired stimuli (n = 6), or no stimuli (n = 6). Autoradiograms were analyzed by measuring binding in strictly defined regions of interest and from transept profiles. A significant increase in binding of the phorbol ester was found in the CA3 stratum oriens in the paired group relative to unpaired and naive controls. No other significant differences were found.The nictitating membrane (NM) conditioned response (CR) is an associative learning model in which rabbits learn to associate a tone (conditioned stimulus, CS) with a shock (unconditioned stimulus, US) to the periorbital region (1, 2). Retraction of the NM in response to the tone (a CR) is used to index the progression of learning. The hippocampus has been shown to be necessary for both proper consolidation of the NM response in undertrained rabbits and proper extinction of the response in overtrained rabbits (3, 4). Firing patterns for CA1 and CA3 pyramidal cells formed a striking "neural model" of the CR during paired NM training (5). Furthermore, changes in neuronal firing within the CA1 and CA3 areas of the hippocampus occurred within the first 10 paired trials and increased throughout the training period (5, 6).Extensive studies of hippocampal neurons have been performed with rabbits that were overtrained using this paradigm and sacrificed 24 hr later. In such rabbits, postsynaptic biophysical changes in CA1 neurons were demonstrated, including increased input resistance (7), decreased after hyperpolarizations (8, 9), and increased summation of postsynaptic potentials (10). Accompanying the biophysical changes at this time point were biochemical changes (11-13), with two studies localizing an increase in membrane-bound protein kinase C (mPKC) to the CAl region (11, 12). Binding of phorbol 12,13-dibutyrate (PBt2) in brain of overtrained rabbits sacrificed 72 hr after completion of training showed P...

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Section: Discussionmentioning

confidence: 94%

Protein kinase C redistribution within CA3 stratum oriens during acquisition of nictitating membrane conditioning in the rabbit.

Scharenberg

Olds

Schreurs

et al. 1991

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

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“…We first measured PKC activity in detergent-solubilized cell homogenates under conditions where enzyme activity varies linearly with enzyme concentration [30]. The total specific activity of PKC in LAN-5 cells rose in a time-dependent manner with the IFN-y treatment, reaching a maximum (approximately twofold the level of untreated cells) after five days of culture (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The supernatant was loaded onto a DEAE-cellulose column and PKC activity was semipurified as described [29]. Total cellular PKC content was determined using histone type III-S as substrate as described [30]. Specific PKC activity is expressed as pmol "P transferred per mg substrate protein per min.…”

Section: Protein Kinase C Activity Assaymentioning

confidence: 99%

Protein kinase C isoenzymes in human neuroblasts involvement of PKCε in cell differentiation

et al. 1993

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Although neuronal cells are a major target of phorbol ester action, the activity of the various protein kinase C (PKC) isoenzymes have not been studied in detail in human neuroblasts. Differentiation of the LAN-5 human neuroblastoma cell line by interferon-y (IFN-y) is accompanied by a twofold increase in PKC activity. Since PKC is a multigene family, we investigated which isoforms were expressed in control and differentiated cells, and which of these isoenzymes is involved in neuronal differentiation. We found that: (1) PKC activity is higher in differentiated than in undifferentiated cells; (2) RT-PCR analysis showed the expression of mRNA for PKCa, -y, -6, -E and -c and the absence of mRNA forp in untreated LAN-5 cells; (3) Western blot evaluation with PKC isoform-specific antibodies showed the same pattern of PKC expression in non-differentiated cells; (4) Expression of PKCE mRNA was significantly enhanced by IFN-y-induced differentiation, while the other isoforms were not affected; (5) Differentiation of LAN-5 cells with IFN-I or retinoic acid induced overexpression of the PKCE protein, while inhibition of cell proliferation by fetal calf serum starvation was without effect. These findings suggest that expression of PKCE isoform is tightly coupled with neuronal differentiation and may play a role in the maintenance of the differentiated state.

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“…mAChRs are primary regulators of PKC translocation/ activation (Van der Zee et al, 1993), nAChRs can also signal through PKC (Messing et al, 1989), and in addition, nAChRinduced release of other neurotransmitters further activate PKC pathways (Wonnacott, 1997). Both the a7 and a4b2 nAChR subtypes are implicated in the cognitive-enhancing effects of nicotine, including those mediated through septohippocampal cholinergic pathways (Rezvani and Levin, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Nicotine therapy has been applied successfully in humans as well as in animal models for the reversal of cognitive dysfunction associated with surgical lesions or neurodegenerative disorders (Rezvani and Levin, 2001), and can be applied safely and continuously either by transdermal patches in humans (Hanson et al, 2003) or by subcutaneously implanted osmotic minipumps in animals (Slotkin, 1998(Slotkin, , 2002. Nicotinic cholinergic receptors crosstalk with muscarinic cholinergic inputs at the level of protein kinase C (PKC) (Messing et al, 1989;Tuominen et al, 1992), providing a rationale for a mechanistically based reversal of phenobarbital-induced neurobehavioral and synaptic defects.…”

Section: Introductionmentioning

confidence: 99%

Nicotine Therapy in Adulthood Reverses the Synaptic and Behavioral Deficits Elicited by Prenatal Exposure to Phenobarbital

Beer

Slotkin

Seidler

et al. 2004

Neuropsychopharmacol

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A major objective in identifying the mechanisms underlying neurobehavioral teratogenicity is the possibility of designing therapies that reverse or offset drug-or toxicant-induced neural damage. In our previous studies, we identified deficits in hippocampal muscarinic cholinergic receptor-induced membrane translocation of protein kinase C (PKC)g as the likely mechanism responsible for adverse behavioral effects of prenatal phenobarbital exposure. We therefore explored whether behavioral and synaptic defects could be reversed in adulthood by nicotine administration. Pregnant mice were given milled food containing phenobarbital to achieve a daily dose of 0.5-0.6 g/kg from gestational days 9-18. In adulthood, offspring showed deficits in the Morris maze, a behavior dependent on the integrity of septohippocampal cholinergic synaptic function, along with the loss of the PKCg response. Phenobarbital-exposed and control mice then received nicotine (10 mg/kg/day) for 14 days via osmotic minipumps. Nicotine reversed the behavioral deficits and restored the normal response of hippocampal PKCg to cholinergic receptor stimulation. The effects were regionally specific, as PKCg in the cerebellum was unaffected by either phenobarbital or nicotine; furthermore, in the hippocampus, PKC isoforms unrelated to the behavioral deficits showed no changes. Nicotine administration thus offers a potential therapy for reversing neurobehavioral deficits originating in septohippocampal cholinergic defects elicited by prenatal drug or toxicant exposures.

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Nicotinic and muscarinic agonists stimulate rapid protein kinase C translocation in PC12 cells

Cited by 67 publications

References 40 publications

Protein kinase C redistribution within CA3 stratum oriens during acquisition of nictitating membrane conditioning in the rabbit.

Protein kinase C redistribution within CA3 stratum oriens during acquisition of nictitating membrane conditioning in the rabbit.

Protein kinase C isoenzymes in human neuroblasts involvement of PKCε in cell differentiation

Nicotine Therapy in Adulthood Reverses the Synaptic and Behavioral Deficits Elicited by Prenatal Exposure to Phenobarbital

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