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Biomedical subjects

M J Wayner

Publications and source records attributed to M J Wayner.

At least 19 recordsLinked to original sources
PubMed1992

Coexistence of autonomic and somatic mechanisms in the pressor areas of medulla in cats.

The effects of electrical stimulation and microinjection of sodium glutamate (0.5 M) in the sympathetic pressor areas of the dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular nucleus (PVC) on the knee jerk, crossed extension, and evoked potential of the L5 ventral root produced by intermittent electrical stimulation were studied in 98 adult cats anesthetized with chloralose and urethane. During electrical and glutamate stimulation of these pressor areas, in addition to the rise of systemic arterial blood pressure marked inhibition of the spinal reflex was produced, indicating presence of neuronal perikarya responsible for these actions. Mild to moderate augmentation of spinal reflexes was also observed during brain stimulation but only in a few cases. The magnitude of the somatic effects among the pressor areas of the VLM, DM, and PVC subsequent to glutamate activation was about the same. Induced spinal reflex inhibition, independent from the baroreceptor and vagal influence, remained essentially unaltered after acute midcollicular decerebration. The inhibition was also observed in cats decerebellated 8-10 days in advance. The inhibition was not affected after bilateral electrolytic- or kainic-acid-induced lesions in the paramedian reticular nucleus (PRN). On the contrary, PRN-induced spinal reflex inhibition was attenuated after bilateral lesions in the DM or VLM. Data suggest that there coexists neuronal subpopulations in the VLM, DM, and PVC that can affect both the sympathetic pressor systems and spinal reflexes.

Animals↗
PubMed1991

Angiotensin II blocks hippocampal long-term potentiation.

We have found that injection of angiotensin II (AII) above the hippocampus in the intact rat blocks the induction of long-term potentiation (LTP) in perforant path-stimulated dentate granule cells. A minimum dose of 4.78 pmol AII was required for the complete blockade of LTP and this blockade was entirely prevented if the AII-specific antagonist saralasin was co-injected at a 50-fold molar excess. AII thus appears to act via AII receptors and does not cause non-specific inhibition. The injection of saralasin alone yielded LTP comparable to that obtained when vehicle was injected. Angiotensin III was found to be 40-50 fold less potent than AII in blocking LTP. Both AII and AII receptors of unknown function occur in the hippocampal formation. The results reported here suggest a role for these molecules in the control of hippocampal LTP.

Amino Acid Sequence↗
PubMed1991

Effects of three reputed carboxylesterase inhibitors upon rat serum esterase activity.

Rats have very high endogenous levels of serum carboxylesterase (CAE) compared to primates. This difference accounts for the lower sensitivity of rats to toxic organophosphates, which interact with CAE instead of the more critical acetylcholinesterase. Pretreatment of rats with CAE inhibitors potentiates the effects of organophosphates. In this study, the effects of three putative CAE inhibitors, 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP), bis-p-nitrophenyl-phosphate (BNPP), and tetraisopropyl pyrophosphoramide (Iso-OMPA), on the hydrolysis of several commercially available substrates were determined. Respective kinetic constants Km and Vmax were derived and effects of inhibitors compared using saturating amounts of substrate. Data presented here indicate significant differences in substrate affinity (Km), reactivity (Vmax), as well as effects of inhibitors. CBDP inhibits hydrolysis of specific naphthyl and paranitrophenyl esters at relatively low concentrations (1-10 microM). In contrast, significantly higher concentrations (mM) of BNPP and Iso-OMPA were required for inhibition of serum esterase activity. Of the inhibitors tested, Iso-OMPA in general exhibited the smallest inhibitory effect on ester hydrolysis. Although inhibition of hydrolysis of specific paranitrophenyl and naphthyl esters occurred in the presence of similar amounts of CBDP, the degree of inhibition differed significantly (50-75% vs. greater than 90%, respectively). These data suggest that there exists in rat serum, a pool of naphthyl ester esterase activity that is very sensitive ex vivo (greater than 90% inhibition) to CBDP and may be very useful in validating a rodent model for soman toxicity.

Animals↗
PubMed1990

Evidence that protein kinase M does not maintain long-term potentiation.

We have shown that the induction but not maintenance of long-term potentiation (LTP) in the Schaffer collateral-CA1 synaptic zone of the rat hippocampus is blocked by the extracellular application of the protein kinase inhibitor staurosporine. This compound was also found to block the induction of LTP in the perforant path-granule cell synaptic zone of the intact hippocampus. We have determined that staurosporine is membrane-permeable and can be detected inside cells by fluorescence microscopy. When cultured fetal hippocampal neurons were treated with staurosporine, fluorescence was observed throughout the cytoplasm and in neurites. Other cell types gave similar results. It has been proposed that constitutively active cytosolic protein kinase M or other protein kinases maintain long-term potentiation. Since staurosporine has access to the cytosol and inhibits protein kinase M in vitro, our results suggest that this enzyme is not responsible for the maintenance of LTP. This conclusion may extend to other protein kinases as well, since staurosporine has been shown to inhibit a variety of these enzymes.

Alkaloids↗
PubMed1990

Calpain inhibitors block long-term potentiation.

Long-term potentiation (LTP) is a form of synaptic plasticity that serves as a model for certain types of learning and memory. The role of the calcium-activated thiol proteases or calpains in the biochemical mechanism of LTP has been explored. We show that the extracellular application of two newly developed, highly potent calpain inhibitors, N-acetyl-Leu-Leu-norleucinal and N-acetyl-Leu-Leu-methioninal, block LTP in both the Schaffer collateral-CA1 synaptic zone of the rat hippocampal slice and in perforant path-stimulated dentate granule cells in the intact hippocampus. The inhibitors do not affect baseline synaptic transmission and block LTP in the slice preparation if applied before but not after tetanic stimulation. The calpain inhibitor leupeptin is less potent than the above peptides but also blocks LTP if applied at a sufficient concentration.

Animals↗
PubMed1990

Inhibition of spinal reflexes by paramedian reticular nucleus.

The inhibitory actions of the paramedian reticular nucleus (PRN), and its neighbouring structures, i.e., midline raphe nuclei (MRN) and dorsal medullary depressor area (DMD) on the knee jerk (KnJ) and crossed extension movement (CEM) induced by central sciatic stimulation and on the L5 ventral root response (EVRR) evoked by central tibial stimulation, were studied in cats under urethane (400 mg/kg) and alpha-chloralose (40 mg/kg) anesthesia alone, IP or further paralyzed with atracurium besylate (0.5 mg/kg/30 min), IV. Electrical stimulation of the above areas with rectangular pulses (80 Hz, 1.0 msec, 100-200 microA) decreased systemic arterial blood pressure (SAP) in an average value of: 36 +/- 3 mmHg for PRN; 19 +/- 2 mmHg for MRN; and 23 +/- 3 mmHg for DMD. The KnJ and CEM were almost completely suppressed by simultaneous PRN stimulation. The EVRR, including mono- and polysynaptic spinal reflexes with transmission velocity from 10 to 60 m/sec or above, were also suppressed. MRN stimulation only inhibited the KnJ, CEM and polysynaptic spinal reflexes with transmission velocities between 25 and 60 m/sec, but facilitated spinal reflexes with conduction velocities below 10 m/sec. On the other hand, DMD stimulation resulted in small suppression of KnJ, CEM and inhibition of polysynaptic spinal reflexes with conduction velocities between 25 and 60 m/sec. Even though MRN and DMD partially inhibited polysynaptic spinal reflexes, the magnitude of such inhibition was much smaller than that produced by PRN (-20% and -22% vs. -48%). The above-mentioned PRN effects on SAP and EVRR persisted in chronic animals decerebellated 9-12 days before.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Vagus nerve afferent and efferent innervation of the rat uterus: an electrophysiological and HRP study.

To determine a possible brainstem connection with the uterus, a study with electrophysiological techniques and horseradish peroxidase (HRP) tracing was performed in the rat. Neurons of the nucleus of the tractus solitarius decreased in discharge frequency during cervicovaginal distension. HRP injections into the uterine walls resulted in the appearance of labelled cells in the nodose ganglion and in the dorsal motor nucleus of the vagus nerve. The results demonstrate a direct bidirectional vagal complex-uterus connection via the vagus nerve. Results are discussed in terms of a complex uterus control system in which the paraventricular nucleus might play an integrative role.

Animals↗
PubMed1988

Olfactory and visceral projections to the nucleus of the solitary tract.

Electrophysiological studies were performed to determine if neurons of the nucleus of the solitary tract (NTS) which receive inputs from the stomach via vagal afferents also respond to olfactory bulb (OB) stimulation. The frequency of neuronal activity of the rostral ventral portion of the NTS was increased by gastric distension (GD). The evoked potentials in the same site due to vagal stimulation displayed short latencies; whereas, the evoked potentials in the dorsomedial part of the NTS due to vagal stimulation had considerably longer latencies. Gastric distension decreased neuronal activity in the dorsomedial NTS. Evoked potentials and increases in neuronal activity were also observed in the dorsomedial NTS due to electrical stimulation. In the dorsomedial NTS, OB stimulation enhanced the decrease in neuronal activity due to GD. Olfactory and visceral functions apparently interact in the NTS in modulating taste mechanisms involved in food selection and ingestion.

Afferent Pathways↗
PubMed1988

Kinetic properties of the [Ca2+ + Mg2+]-ATPase in Alzheimer and normal fibroblasts at low free calcium.

Kinetic properties of the [Ca2+ + Mg2+]-ATPase from one Alzheimer (AG0364B, 53-year-old donor) and one control fibroblast cell line (AG6009, 59-year-old donor) were examined. A saturation plot revealed the control fibroblast ATPase activity to saturate at approximately 500 nM free Ca2+; whereas, the Alzheimer activity saturated at approximately 1000 nM. Eadie Hofstee graphical analysis indicated almost identical Vmax values, 19.5 and 21.0 nmoles phosphate released/min/mg protein for the Alzheimer and control fibroblasts, respectively. However, an approximately two-fold higher Km value of 350 nM was observed for the Alzheimer fibroblast homogenate in contrast to 220 nM for the control. In a previous study, a kinetic difference in Alzheimer fibroblast [Ca2+ + Mg2+]-ATPase activity at high free Ca2+ concentration was observed. The difference in affinity reported in this study at low free Ca2+ concentrations supports further the hypothesis that abnormalities in Ca2+ homeostasis might be involved in the etiology of Alzheimer's disease.

Alzheimer Disease↗
PubMed1988

Olfactory and visceral projections to the paraventricular nucleus.

Electrophysiological studies were performed to determine if neurons of the paraventricular nucleus (PVN) which receive inputs from the stomach via vagal afferents also respond to nucleus of the solitary tract (NTS) and olfactory bulb (OB) stimulation. We found that the NTS, OB stimulation, and gastric distension depress the firing frequency of PVN neurons. The pathway from the NTS to the PVN contains larger fibers than the projection from the PVN to the NTS.

Action Potentials↗
PubMed1987

Partial characterization of two (Ca+2 + Mg+2)-dependent ATPase activities from bovine brain synaptic membrane homogenates.

Synaptic plasma membranes isolated from bovine brain exhibited a low and high affinity (Ca+2 + Mg+2)-dependent ATPase as evidenced by kinetic constants for ATP. One activity which hydrolyzed ATP maximally at pH 7.4 and 7.8 exhibited an 8-fold higher affinity when compared to the second or lower affinity activity which hydrolyzed ATP maximally at pH 7.0. Both activities exhibited submicromolar kinetic constants for Ca+2 (Km = 0.24 micromolar). Km values for magnesium differed significantly; the lower affinity activity being approximately 6.5 times higher (120 microM) than that observed for the high affinity activity (18 microM). Vmax values obtained under optimal assay conditions (low and high) were 110-135 and 43-55 nmol/min/mg protein, respectively. Both activities were KCN, NaN3 and ruthenium red insensitive. Only slight inhibition was observed in the presence of rotenone and oligomycin. Although both activities were observed to be trifluoperazine sensitive, they differed significantly with regard to other parameters. Na+1 and NH4+1 ions preferentially inhibited the low affinity activity greater than 90%. Cs+1 ions completely inhibited the high affinity activity while reducing the low affinity only 22%. Li+1, Al+3 and Mn+2 significantly inhibited the high affinity activity while reducing the low activity only moderately. Both the low and high activity were inhibited by vanadate with half maximum inhibition occurring at 2 and 5 microM, respectively indicating the plasma membrane origin of these activities. Thermal denaturation studies indicated the high affinity activity to be stable for 2 minutes at 45 degrees C after which 50% of the activity is lost at 2.5 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The effects of trimethyltin on the Ca+2, Mg+2 and Ca+2 + Mg+2-dependent ATPases of human neuroblastoma GM 3320.

Data presented here indicate neuroblastoma GM 3320 tissue homogenates exhibit ouabain insensitive Ca+2-dependent, Mg+2-independent, Mg+2-dependent, Ca+2-independent and Ca+2 + Mg+2-dependent ATPase activities. Inclusion of trimethyltin in homogenate preparations of these cells appears to discriminate between these various ATPase activities. At low concentrations (25 microM), trimethyltin preferentially stimulated the Ca+2-dependent, Mg+2-independent ATPase activity while inhibiting the Ca+2 + Mg+2-ATPase activity approximately 70%. At 75 microM trimethyltin, the Ca+2 + Mg+2-dependent ATPase activity is inhibited greater than 95% while the Ca+2-dependent, Mg+2-independent activity is essentially unchanged from control activity and the Mg+2-dependent, Ca+2-independent activity is inhibited approximately 50%. At concentrations greater than 75 microM, trimethyltin significantly inhibits the Ca+2-dependent, Mg+2-independent ATPase activity. Thus, at trimethyltin concentrations of 50-75 microM, preferential inhibition of the Mg+2-dependent, Ca+2-independent and Ca+2 + Mg+2-dependent ATPase activities of neuroblastoma GM 3320 is achieved.

Adenosine Triphosphatases↗
PubMed1986

The effects of purified Mojave toxin on rat synaptic membrane (Ca+2 + Mg+2)-ATPase and the dihydropyridine receptor.

Effects of purified Mojave toxin on rat synaptic membrane (Ca+2 + Mg+2)-ATPase and dihydropyridine receptor were determined. The toxin was observed to stimulate specifically (Ca+2 + Mg+2)-ATPase approximately two-fold with no effect on Mg+2 dependent ATPase activity. Examination of the effects of increasing amounts of purified Mojave toxin on binding of the calcium channel blocker, nitrendipine, indicated that the addition of 10 micrograms (4.5 X 10(-10) moles) of toxin resulted in greater than 90% inhibition of nitrendipine binding. Furthermore, binding studies revealed the toxin to have little affinity for the ligand indicating its interaction with calcium channel components. Since Mojave toxin has associated with it a phospholipase A2 activity, we investigated the effects of 4-bromophenacylbromide, a known inhibitor of phospholipase A2 activity in order to discern the possible effects of the purified toxin on synaptic membranes. At concentrations previously shown to be inhibitory of purified phospholipase A2 from cobra venom, both ATPase activity and nitrendipine binding of synaptic membranes were significantly inhibited. Thus we cannot rule out the possibility that the endogenous phospholipase activity of the purified toxin is responsible for its effects on the rat brain synaptic functions studied here. Binding studies conducted in the presence of verapamil and diltiazem indicated that the toxin interacts with allosteric sites responsible for regulation of the binding of nitrendipine. Although we have not tested the effects of Mojave toxin on other ion channels and/or receptors, results presented here suggest the potential usefulness of this toxin as a molecular probe of the calcium channel complex.

Animals↗
PubMed1985

Direct effects of androgens on lateral hypothalamic neuronal activity in the male rat: I. A microiontophoretic study.

Unit neuronal activity in the lateral hypothalamic-medial forebrain bundle region (LHA-MFB) of the male rat is modified following an increase of plasma testosterone level. In order to determine possible direct action of hormones on LHA-MFB neurons, unit discharge frequencies were recorded during local microiontophoresis of testosterone and estradiol, and electroosmotic application of cholesterol. Thirteen cells did not respond, 9 were nonspecifically depressed by all the steroids tested, 13 were excited by both sex-steroids, and 11 were specifically activated by testosterone. The short latencies of the responses suggest a direct effect of steroids on the plasma membrane sites.

Action Potentials↗
PubMed1985

Olfactory bulb neurons respond to gastric distension.

Single unit discharges in the olfactory bulb (OB) were recorded extracellularly in anesthetized rats during controlled gastric distension. The activity of 37 neurons in the periglomerular layer of the OB modulated by gastric distension was analyzed. Twelve of the 37 cells decreased, eight decreased and then increased in frequency, and 17 displayed more complex effects due to gastric distension. Generally, the latency of the responses to gastric distension was less than one second. All those cells which responded to gastric distension also responded to vagus nerve stimulation. This effect was abolished or attenuated by cutting the vagus nerve at the cervical level. The threshold volume by which the stomach was infused for the initial decrease in OB neuronal discharge frequency was 3.0 ml. When more than 8 ml were infused, increases in firing frequencies were always observed. The results of the present experiments indicate that the discharge frequency of the periglomerular OB neurons are modulated by visceral afferents.

Action Potentials↗
PubMed1985

Effects of dopamine and norepinephrine on neuronal activity of the olfactory tubercle.

The effects of iontophoretic administration of norepinephrine (NE) and dopamine (DA) on olfactory tubercle (OT) neurons that respond to lateral hypothalamus (LH) or locus coeruleus (LC) electrical stimulation were studied. NE and DA decreased the frequency of OT neurons which were increased or decreased by the LH stimulation. An increased firing of OT neurons following NE or DA administration was less frequently observed. NE administration decreased the firing of OT neurons that responded to LC stimulation. These results suggest that the LC fibers which reach the OT use NE as a neurotransmitter. DA administration also suppressed the unitary discharge of OT neurons responding to LC stimulation. The increase in frequency of OT neurons observed following LH stimulation cannot be attributed to DA. The possibility that other suspected neural transmitters are involved in this effect is discussed.

Animals↗