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N J Pontzer

Publications and source records attributed to N J Pontzer.

9 recordsLinked to original sources
PubMed1992

Concentrations of carbachol stimulating phosphoinositide hydrolysis cause a sustained decrease in membrane potential and firing rate: role of inositol and inositol polyphosphate second messengers.

We have investigated the relationship between muscarinic agonist-stimulated phosphoinositide (PI) hydrolysis and electrophysiological responses in rat hippocampal slice preparations. In a previous extracellular study, we found that muscarinic agonists at concentrations that stimulate PI hydrolysis result in a biphasic firing response; an initial increase in firing followed by loss of firing at higher concentrations. To test the hypothesis that variability in obtaining consistent loss of firing is related to depletion of intracellular inositol, we investigated the effects of adding exogenous inositol to the buffer. We now report that concentrations of inositol similar to those in cerebral spinal fluid (30-100 microM) augment carbamylcholine (carbachol, CCh) mediated loss of firing and [3H]inositol-1,3,4,5-tetrakisphosphate ([3H]Ins(1,3,4,5)P4) formation. Inhibition of firing produced by 30 microM CCh in the presence of inositol was associated with a sustained depolarization of 20-25 mV, an increased slope resistance in the depolarized range (-60 to -40 mV), and a parallel shift in the hyperpolarized (-100 to -70 mV) range of the voltage-current curve and increased frequency of spontaneous IPSPs. Under voltage-clamp, measurements of the M-current (IM) showed sustained inactivation by CCh with reversal after washout of CCh. Manual depolarization of cells by current injection to the same level of depolarization as attained with CCh did not usually lead to the same loss of firing. These findings suggest that IM, and possibly other voltage-independent currents or ion pumps, may cause loss of firing only in part through a depolarization blockade of firing and not through desensitization. Furthermore, CCh treatment without inositol did not depolarize neurons as much as CCh with inositol, and usually did not cause a delayed loss of firing. Brain slice preparations may thus require physiological concentrations of inositol to show consistent or maximum phosphoinositide-mediated electrophysiological responses.

Action Potentials↗
PubMed1990

Receptors, phosphoinositol hydrolysis and plasticity of nerve cells.

Excitatory amino acid neurotransmission has been shown to be necessary but may not be sufficient, for the production of LTP and other prolonged changes in synaptic transmission. Excitatory neurotransmission may produce depolarization-induced increases in intracellular calcium that cause PI hydrolysis and synergistically potentiate receptor-G protein induced PI hydrolysis. This synergistic potentiation of phosphoinositide hydrolysis, and increased [Ca]i due to positive cross stimulation, may lead to depolarization block, a persistent increase in protein kinase activation, altered morphology, oncogene activity and other plasticity changes important in memory.

Animals↗
PubMed1990

Desensitization of muscarinic stimulated hippocampal cell firing is related to phosphoinositide hydrolysis and inhibited by lithium.

The potency and efficacy of a series of muscarinic agonists for stimulation of neuronal firing rate was compared with stimulation of phosphoinositide (PPI) hydrolysis in similar hippocampal slice preparations. Carbachol, muscarine, pilocarpine, arecoline, bethanechol and oxotremorine varied in potency, but stimulated neuronal firing to a similar extent. At higher concentrations, all of the drugs except oxotremorine caused a decrease in firing rate (desensitization). A comparison of the concentration-response curves for PPI hydrolysis and neuronal firing rates showed that desensitization occurred at a threshold level of PPI hydrolysis. Although the concentration of drug that caused the decrease in firing rate was different for each agonist, the level of PPI hydrolysis at the desensitizing concentration was similar, with the exception of oxotremorine. Oxotremorine, the weakest agonist for stimulation of PPI hydrolysis, did not reach this PPI hydrolysis threshold and did not exhibit desensitization. Oxotremorine was also capable of both blocking and reversing the desensitization caused by carbachol. Low concentrations of pirenzepine, an M1 selective muscarinic antagonist, reversed carbachol desensitization. Concentrations of lithium that disrupt the phosphoinositide cycle by preventing recycling of free inositol (Allison, J. H., et al.: Biochem. Biophys. Res. Commun. 71: 664-670, 1976; Hallcher, L. M. and Sherman, W. R.: J. Biol. Chem. 225: 10896-10901, 1980) slowly reversed desensitization. Furthermore, inositol added to the buffer could re-establish desensitization in lithium-treated preparations. These studies suggest that muscarinic desensitization of hippocampal cell firing is related to large increases in phosphoinositide hydrolysis. Muscarinic receptor-stimulated increases in cell firing may be mediated by a subtype or state of muscarinic receptor different from that mediating phosphoinositide hydrolysis and desensitization.

Action Potentials↗
PubMed1987

Inhibition of heterosensory thalamocortical evoked potentials by delta-9-tetrahydrocannabinol.

The effects of delta-9-tetrahydrocannabinol on sensory activity in the thalamic intralaminar nuclei, centralis lateralis and the mesencephalic reticular formation were compared with the effects on cortical association or heterosensory systems in alpha-chloralose-anesthetized cats. The drug depressed the anterior marginal responses to multiple-modality sensory stimulation 30 min after administration of 2 mg/kg. Posterior suprasylvian responses were not significantly depressed except during 15 min postadministration. The drug did not depress sensory responses at the centralis lateralis or the mesencephalic reticular formation. Cortical responses evoked by stimulation of the latter were globally depressed by the drug. In contrast, delta-9-tetrahydrocannabinol depressed the anterior marginal response to centralis lateralis stimulation and not the posterior suprasylvian response similarly to the responses to sensory stimulation. The drug was without effect on caudate nucleus responses to stimulation of the mesencephalic reticular formation or centralis lateralis. These data demonstrate that, unlike pentobarbital, delta-9-tetrahydrocannabinol maintains heterosensory afferent activity to mesencephalic and thalamic sites and that its unique properties appear to be due, in part, to the selective disruption of heterosensory thalamocortical function.

Acoustic Stimulation↗
PubMed1987

The actions of THC on the intact hippocampus: a comparison of dentate and CA1 responses.

The effects of delta-9-tetrahydrocannabinol were compared on two afferent pathways of the rat hippocampal formation in urethane-anesthetized and chronically implanted awake animals. In urethane-anesthetized rats, THC produced a shift to the right in the input/output relationship without altering the relation between the measures of synaptic wave and the population spike of the CA1 response to contralateral CA3 stimulation. In contrast, the dentate response to perforant path stimulation was not altered by THC. Awake rats exhibited a similar response to THC, however, the CA1 response was less sensitive to THC and there was no change in the maximal response as there was in the anesthetized rat. Paired pulse studies demonstrated that there was a significant increase in paired pulse inhibition at 8 mg/kg in the CA1 region. There was no significant alteration of the dentate response to perforant path stimulation in the awake rat. These results suggest that alterations in limbic electrophysiology induced by THC may be mediated by structures other than the hippocampus.

Animals↗
PubMed1986

Alteration of electrical correlates of sensory processing by tetrahydrocannabinol.

The action of tetrahydrocannabinol on the function of four multimodality responsive neocortical areas was assessed in the cat. Cats, anesthetized with alpha-chloralose, were subjected to auditory, somatosensory, and two types of visual stimulation. Simultaneous evoked field potentials and multiple-unit activity were recorded. The drug produced a significant reduction in evoked field responses at the three most rostral cortical areas, whereas responses at the posterior suprasylvian gyrus were spared. There were no significant differences between sensory modalities. In addition to being the first pharmacological study to demonstrate differential drug sensitivity between these polysensory areas, these studies localized an effect of tetrahydrocannabinol. Sensory evoked multiple-unit activity showed a pattern of change after THC consistent with a reduction in activity of pyramidal output cells and a concomitant increase in interneuron activity. The action of tetrahydrocannabinol on polysensory systems is important in attention and orientation.

Animals↗
PubMed1977

Determination of N1-methylnicotinamide in urine by high-pressure liquid chromatography.

This paper reports a precise method that is shorter than previously reported methods for the quantitative determination of N1-methylnicotinamide (MNA) in urine. The method employs a single column chromatographic isolation step, followed by high-pressure liquid chromatographic (HPLC) analysis. Potential interfering substances present in urine are removed during the column chromatography step. The combined MNA fractions eluted from this column were collected and concentrated for quantitative assay of MNA by HPLC. HPLC analysis was effected in less than 15 min using a strong cation- exchange column eluted with 0.25 M ammonium dihydrogen phosphate (pH 4.3). Linearity of MNA detection by HPLC at 254 nm extended below 20 ng, with an average recovery of 101% for 150, 250 and 500 microgram MNA added to 5 ml or urine.

Chromatography, High Pressure Liquid↗