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Biomedical subjects

M J Wayner

Publications and source records attributed to M J Wayner.

At least 37 records · Page 2Linked to original sources
PubMed1994

GABA inhibition of lateral hypothalamic neurons: role of reticular thalamic afferents.

GABA and reticular thalamic (RT) stimulation induced inhibition of lateral hypothalamic (LH) neuronal activity was studied to determine if RT inhibitory input to the LH is mediated by stimulation of GABA receptors. Seven barrel electrodes were utilized to record simultaneously from the LH during microiontophoretic application of GABA, glycine, bicuculline, picrotoxin, and electrical stimulation of the RT. GABA produced an ejection current-related decrease in LH neuronal activity that was antagonized, in a dose-related manner, by the simultaneous administration of picrotoxin or bicuculline. LH neurons were much less sensitive to glycine inhibition which also was relatively insensitive to the GABA receptor antagonists. RT electrical stimulation provided a short latency inhibitory input to LH neurons that was mimicked by the microiontophoretic administration of GABA. In addition, the microiontophoretic application of picrotoxin or bicuculline blocked the RT stimulation induced inhibition of LH neuronal activity. These data indicate that the inhibitory effects of both GABA and RT synaptic inputs onto LH neurons are mediated by stimulation of GABAA receptors and substantiates the involvement of GABA as the inhibitory transmitter of thalamic to hypothalamic projections.

Animals↗
PubMed1994

Activation of neurons in cardiovascular areas of cat brain stem affects spinal reflexes.

In 65 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg), the effects of electrical stimulation and microinjection of sodium glutamate (0.25 M, 100-200 nl) in the pressor areas in the rostral brain stem on the evoked L5 ventral root response (EVRR) due to intermittent stimulation of sciatic afferents were compared to stimulating the dorsomedial (DM) and ventrolateral (VLM) medulla. In general, stimulating these rostral brain stem pressor areas including the diencephalon (DIC) and rostral pons (RP) produced increases in systemic arterial pressure (SAP). In most of the cases (85%) there were associated changes in the EVRR, predominantly a decrease in EVRR (72%). Stimulation of the midbrain (MB, principally in the periaqueductal grey) produced decreases in SAP and EVRR. Decreases in EVRR was observed in 91% of the DM and VLM stimulations in which an increase in SAP was produced. This EVRR inhibition was essentially unaltered after acute midcollicular decerebration. Increases in EVRR were also observed and occurred more often in the rostral brain stem than in the medulla. Since changes of both EVRR and SAP could be reproduced by microinjection of Glu into the cardiovascular-reactive areas of the brain stem, this suggests that neuronal perikarya in these areas are responsible for both actions. On some occasions, Glu induced changes in EVRR but not in SAP. This effect occurred more frequently in the rostral brain stem than in the medulla. The present data suggest that separate neuron population exist in the brain stem for the integration of SAP and spinal reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Angiotensin AII AT1 receptor mediates ethanol-diazepam inhibition of hippocampal LTP.

Within a limited range of doses, co-administration of ethanol (EtOH) and diazepam (DZ) produce enhanced anxiolytic effects. These combined effects on long-term potentiation (LTP) in the hippocampus of rats anesthetized with urethane were studied in an attempt to provide an explanation at a more fundamental neuronal level. Male Sprague-Dawley rats received 0.1, 0.5, 0.75 and 1.0 mg/kg DZ i.p. in combination with 0.1, 0.5, 0.75 g and 1.0 g/kg EtOH by gavage, respectively. Drugs were administered 20 min (EtOH) and 15 min (DZ) prior to tetanic stimulation of the medial perforant path which resulted in LTP induction measured in terms of the relative change in amplitude of the population EPSP as compared to baseline. Effects of both drugs alone and in combination on LTP are presented. Both drugs depressed LTP induction and significant enhanced interactive effects were observed. We have previously shown that angiotensin II (AII) inhibits LTP induction and that the inhibition can be blocked by losartan, an AII AT1 receptor antagonist. Our present results demonstrate that the combined inhibitory effects of EtOH and DZ on LTP induction are also blocked by losartan.

Angiotensin II↗
PubMed1993

Role of angiotensin II and AT1 receptors in hippocampal LTP.

Results of a previous study showed that angiotensin II (AII) inhibited the induction of long-term potentiation (LTP) in hippocampal granule cells in response to dorsomedial perforant path stimulation in urethane-anesthetized rats. The results of present experiments demonstrate a dose-dependent inhibition of LTP induction under the same conditions due to ethanol (EtOH) administered by stomach tube and diazepam (DZ) injected IP. The inhibition of LTP induction by EtOH and DZ can be blocked by saralasin (SAR) applied directly to the dorsal hippocampus and by lorsartan (DuP 753) administered IP. Lorsartan or a metabolite crosses the blood-brain barrier because it also blocks the inhibition of LTP induction due to AII administration directly into the dorsal hippocampus. Lorsartan is a competitive antagonist of the AT1 subtype AII receptor. Therefore, the AII and the EtOH and DZ inhibition of LTP induction are mediated by the AII subtype receptor AT1. AIII and the AT2 antagonist PD123319 did not produce any significant effects. These in vivo effects can be reproduced in brain slices and therefore cannot be attributed to other factors, such as the urethane. In addition, electrical stimulation of the lateral hypothalamus (LH) inhibits LTP induction, and the inhibition can be blocked by SAR. These data on LH stimulation indicate that LH AII-containing neurons send axons into the hippocampus that inhibit the induction of LTP. These results not only provide new information on a neurotransmitter involved in the amnesic effects of benzodiazepines and ethanol-induced memory blackouts, but also testable hypotheses concerning recent observations that angiotensin converting enzyme (ACE) inhibitors elevate mood and improve certain cognitive processes in the elderly.

Angiotensin II↗
PubMed1993

Olfactory bulb neurons respond to cervicovaginal distension.

Mitral cell layer neuronal activity in the olfactory bulb (OB) of the anesthetized rat is modulated by cervicovaginal distension. Data are reported on 22 cells that decreased and 6 that increased in response to the distension. These results provide support for the existence of a functional interaction between the reproductive tract and the olfactory system.

Animals↗
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↗