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J J Kendig

Publications and source records attributed to J J Kendig.

At least 37 records · Page 2Linked to original sources
PubMed1995

Selective effects of ketamine on amino acid-mediated pathways in neonatal rat spinal cord.

Many ion channels have been proposed as target sites for anaesthetic action; for some agents multiple receptors-ion channels may be implicated. In addition to acting as a non-competitive antagonist at glutamate NMDA receptors, ketamine also affects other ion channels. The present study was undertaken to determine if the effects of ketamine in an integrated portion of the central nervous system involve multiple actions at glutamate non-NMDA, glutamate NMDA, and GABAA receptor. The effects of ketamine 1-50 mumol litre-1 were examined on three pharmacologically distinct responses in isolated superfused neonatal rat spinal cord: the monosynaptic reflex (glutamate non-NMDA); a slow ventral root potential (VRP) with a large NMDA-mediated component; and the dorsal root potential (DRP) (GABAA). Ketamine, at concentrations relevant to anaesthesia (1-50 mumol litre-1), reversibly depressed the area under the curve of the slow VRP in a concentration-dependent fashion. The effects of ketamine were selective for the early (0-1 s) component of the slow VRP. The monosynaptic reflex was unaffected at these concentrations. The actions of ketamine resembled those of the NMDA antagonist APV. Dorsal root potentials evoked by dorsal root stimulation or by muscimol were either unaffected or reversibly depressed by ketamine 1-20 mumol litre-1. The concentrations tested include the anaesthetic range for both rats and humans. The effects of ketamine on neurotransmission in this preparation can be accounted for entirely by its action at NMDA receptors. Glutamate non-NMDA receptors were unaffected and GABAA transmission was not enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Selective effects of alfentanil on nociceptive-related neurotransmission in neonatal rat spinal cord.

We have examined the effects of alfentanil on nociceptive-related neurotransmission in isolated neonatal rat spinal cord, with particular attention to acute tolerance. Electrical stimulation of a lumbar dorsal root was used to evoke the monosynaptic reflex (MSR), a slow ventral root potential (sVRP), and the dorsal root potential (DRP). Alfentanil (0.5 nmol litre-1 to 1 mumol litre-1) depressed sVRP area by a maximum of 85%; EC50 was approximately 2 nmol litre-1. The effects of alfentanil were selective for very slow, metabotropically mediated sVRP components compared with faster NMDA receptor-mediated components. The MSR was unaffected. Alfentanil depressed DRP area by a maximum of 50% at 1 mumol litre-1. Naloxone antagonized all alfentanil effects. Morphine depressed sVRP area with an approximate EC50 of 90 nmol litre-1, giving an alfentanil:morphine potency ratio of 45:1. The effects of alfentanil on sVRP showed no biphasic time dependence up to 60 min. Naloxone administered after alfentanil produced a significant rebound in sVRP area to a level of 143 (SD 21.3)% above control. Thus, in this study there was no evidence for acute tolerance, as measured by a decrease in effectiveness over time, but there was evidence as measured by rebound following naloxone.

Alfentanil↗
PubMed1995

Long-term potentiation in an isolated peripheral nerve-spinal cord preparation.

1. Long-lasting increases in synaptic efficacy following repetitive stimulation have been demonstrated at several sites in the CNS, where they are collectively termed long-term potentiation (LTP). LTP is of interest with respect to its presumptive relationship to learning and memory in hippocampus. In the spinal cord in vivo, an LTP-like phenomenon is thought to underlie the allodynia and hyperalgesia that follows some peripheral injuries. 2. We investigated the capacity of the isolated neonatal rat spinal cord to sustain a long-lasting increase in a nociceptive-related slow ventral root potential (sVRP) recorded from a lumbar root after a tetanic train of stimuli to the peripheral cutaneous saphenous nerve. Stimuli were delivered at a low constant (0.02 s-1) frequency during a 30-min control period. A tetanic stimulus train (10 s-1 for 60 s) was then given followed by a resumption of low (0.02 s-1) frequency stimulation. Potentiation was defined as an increase in sVRP area > 2 SD above control mean. 3. Twenty of 20 preparations showed immediate posttetanic potentiation. In 13 of the 20, potentiation was maintained for > or = 1 h after the tetanic stimulus train. 4. Potentiation was dependent on activation of C fibers during the inducing train; stimuli below C-fiber threshold, activating only A fibers, were ineffective. Potentiation was selectively expressed by a long-latency component of the sVRP elicited by stimuli at a strength that evoked both A- and C-fiber responses in the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Correlates of anesthetic properties in isolated spinal cord: cyclobutanes.

Two halogenated cyclobutanes, one anesthetic and one not, were compared on receptor-specific pathways in isolated neonatal rat spinal cord. The anesthetic 1-chloro-1,2,2-trifluorocyclobutane depressed the monosynaptic reflex (glutamate non-NMDA receptors) and abolished a slow ventral root potential (glutamate NMDA, non-NMDA and tachykinin receptors). This compound slightly enhanced the muscimol-evoked dorsal root potential (GABAA) but reversibly depressed the dorsal root potential elicited by dorsal root stimulation. The non-anesthetic 1,2-dichlorohexafluorocyclobutane increased monosynaptic reflex, depressed slow ventral root potential approximately 50%, had little effect on muscimol-evoked dorsal root potential, and irreversibly depressed dorsal root-evoked dorsal root potential. Hypoxia accounts for slow ventral root potential depression, but not monosynaptic reflex enhancement. In this preparation and for this pair of compounds, anesthetic properties are related to blockade of transmission at glutamate synapses, with a small component of GABAA enhancement. Monosynaptic reflex increase may be related to the non-anesthetic cyclobutane's convulsant and anti-anesthetic properties.

Anesthesia↗
PubMed1992

Substance P and NMDA receptor-mediated slow potentials in neonatal rat spinal cord: age-related changes.

Slow ventral root potentials (slow VRP's) recorded from 1- to 5-day-old rat spinal cords are implicated in nociception, but there is controversy over their origin and persistence in the adult. The present study investigated changes in the role of substance P and NMDA receptors in slow VRP generation during the postnatal period (1-21 days). Through 9 days, dorsal root stimulation elicits slow VRP's with typical peak amplitudes at 3-4 s, decay time constants of 18-20 s, and durations > 20 s. After 11 days, peak amplitude shortens to < 1 s, decay time constant 4-5 s, and duration < 10 s. At 1-6 days, slow VRP's are sensitive to the NMDA receptor antagonist APV and the substance P antagonists spantide and CP 96,345. After 11 days, APV sensitivity is retained, but spantide and ability of substance P to evoke a response are diminished. Abbreviated slow VRP's in post-11-day spinal cords appear to correspond to the early APV-sensitive component of long-duration slow VRP's in younger animals. Attempts to restore long-duration slow VRP's in 12- to 14-day-old rat cords by blocking various inhibitory mechanisms were not successful. The results suggest that a substance P response, some of which is mediated by NK1 receptors, is lost with maturation of the cord. Either a developmental role played by substance P changes with maturity, or the motor neurons of the isolated post-11-day cord lose the capacity to sustain large long-duration plateau potentials.

2-Amino-5-phosphonovalerate↗
PubMed1992

Propofol and barbiturate depression of spinal nociceptive neurotransmission.

Barbiturates are often described as non-analgesic or even hyperalgesic agents; the newer intravenous anesthetic agent propofol is said to be non-analgesic. Both propofol and barbiturates occupy sites on the GABAA receptor. The present study was designed to compare the effects of propofol and barbiturates on nociceptive-related neurotransmission in neonatal rat spinal cord; to search for actions that might be hyperalgesic; and to determine the extent to which propofol depression of nociceptive neurotransmission is mediated by GABAA receptors. The monosynaptic reflex, a slow ventral root potential (slow VRP) and the dorsal root potential (DRP) were recorded from isolated neonatal (1-5 days old) superfused rat spinal cords in response to electrical stimulation of a lumbar dorsal root. The slow VRP and the DRP are related to nociception. Propofol (0.5-10 microM), pentobarbital (1-10 microM), and thiopental (1-10 microM) reversibly depressed the slow VRP. Dose-response curves were monophasic and linear over this range. The monosynaptic reflex was unaffected. The GABAA agonist muscimol (0.2-1 microM) also depressed the slow VRP. Propofol and barbiturate slow VRP depression was antagonized by the GABAA antagonist bicuculline (1 microM). Propofol depressed the response evoked by direct application of substance P. The DRP is a GABAA-mediated depolarization of primary afferent nerve terminals that diminishes the effectiveness of nociceptive input. Propofol and thiopental increased electrically evoked DRP amplitude and increased the DRP evoked by application of muscimol. Both propofol and barbiturates thus depressed the nociceptive-related slow VRP and enhanced the antinociceptive DRP; their effective concentrations are at or close to the general anesthetic range for these agents. No anti-analgesic or hyperalgesic effect was observed. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Substance P and NMDA receptors mediate a slow nociceptive ventral root potential in neonatal rat spinal cord.

Substance P and glutamate actions have separately been implicated in the generation of nociceptive-related slow ventral root potentials (slow VRPs). We report that slow VRPs are dependent on both substance P and NMDA receptor-mediated neurotransmission. Slow VRPs of 10-40 s duration were evoked by electrically stimulating a lumbar dorsal root and recorded at the corresponding ipsilateral ventral root in spinal cords isolated from 1- to 5-day-old rats; the monosynaptic reflex was also recorded. The NMDA receptor antagonist APV (5-20 microM) and the substance P antagonist spantide (10-20 microM) both reversibly depressed the slow VRP without affecting the monosynaptic reflex; spantide and APV applied together nearly abolished the slow VRP. The quisqualate-kainate receptor antagonist CNQX (1-5 microM) reduced the monosynaptic reflex and an early component of the slow VRP. A slow VRP could be elicited by brief (0.1-1.0 s) focal applications of either substance P (2-20 microM) or NMDA (10 microM), and also by CGRP (2-20 microM). Substance P-evoked and NMDA-evoked responses were blocked by their respective antagonists spantide and APV. Each was also cross-sensitive to the other antagonist. Both excitatory amino acids, acting on an NMDA receptor, and substance P, acting on a tachykinin receptor, thus appear to be involved in generating this slow potential. Both NMDA and tachykinin receptors are necessary to generate a full response.

2-Amino-5-phosphonovalerate↗
PubMed1991

The alpha 2-adrenoceptor agonist dexmedetomidine increases the apparent potency of the volatile anesthetic isoflurane in rats in vivo and in hippocampal slice in vitro.

Alpha 2-adrenoceptor agonists such as clonidine are sedatives and enhance the effectiveness of several different kinds of anesthetics. This study was performed to quantitate the effect of dexmedetomidine, a novel alpha 2-adrenoceptor agonist, on the action of the volatile anesthetic agent isoflurane in rats in vivo. A separate set of experiments in rat hippocampal slices was designed to determine whether isoflurane and dexmedetomidine exerted similar effects on synaptic transmission in vitro and to examine the interaction between the two agents. In vivo, dexmedetomidine (100 micrograms/kg i.p.) reduced isoflurane minimum alveolar anesthetic requirement (MAC), determined by loss of response to tail pinch, by approximately 90%. In hippocampal CA1 neurons, on the other hand, there was a relatively small potentiation of the effects of isoflurane at the maximally effective dexmedetomidine concentration (1 nM). The hippocampal CA1 area, at least in the slice preparation, may thus not be representative of the CNS site(s) at which alpha 2 adrenoceptor agonists lessen anesthetic requirement in vivo.

Adrenergic alpha-Agonists↗
PubMed1991

Alpha 2-adrenoceptors inhibit a nociceptive response in neonatal rat spinal cord.

Alpha 2-Adrenoceptors mediate analgesia in vivo. The present study explored the actions of the alpha 2-adrenoceptor agonists dexmedetomidine and clonidine on a nociceptive response in isolated neonatal rat spinal cord. Stimulation of a dorsal root generates a slow ventral root potential (slow VRP) at the corresponding ipsilateral ventral root. The slow VRP meets several criteria for a nociceptive response. Dexmedetomidine (10 nM) and clonidine (200 nM) depressed the slow VRP by approximately 80%. Dexmedetomidine's action was approximately linear over the concentration range 0.5-500 nM, whereas clonidine (20 nM-5 microM) exerted biphasic effects. The profile of agonist and antagonist effectiveness characterized the receptor(s) as alpha 2-adrenoceptors; the subtype could not be identified as either alpha 2A or alpha 2B. Naloxone pretreatment partially blocked dexmedetomidine's effect, suggesting a possible endogenous opiate involvement. Dexmedetomidine (0.5-2.0 nM) also depressed the VRP evoked by application of substance P to the cord, implicating postsynaptic as well as possible presynaptic actions. At high concentrations, dexmedetomidine (50-500 nM) depressed the monosynaptic reflex, probably through non-alpha 2-receptor(s). Results from the neonatal spinal cord correlate well with those from in vivo analgesia studies. They suggest an important direct spinal contribution to alpha 2-adrenoceptor-mediated analgesia.

Adrenergic alpha-Agonists↗
PubMed1991

Barbiturate alteration of respiratory rhythm and drive in isolated brainstem-spinal cord of newborn rat: studies at normal and hyperbaric pressure.

High pressure and anaesthetic agents are mutual antagonists in intact animals, but antagonism is not observed in isolated nerve cells. In order to test the hypothesis that a neural network might display pressure-anaesthetic antagonism not found in simpler systems, we have examined the effects of pentobarbitone at normal pressure and at 10.1 MPa helium pressure on the rhythmic activity of medullary respiratory centres of isolated brainstem and spinal cord from 0-3 day old rats. Pentobarbitone 5-80 mumol litre-1 depressed the frequency, amplitude and area of spontaneous bursts recorded from C5, reduced respiratory drive, and altered the response to trigeminal nerve root stimulation. Compression to 10.1 MPa decreased ventilatory frequency and respiratory drive, and either did not interact with or enhanced the depressant effects of pentobarbitone. Pentobarbitone and helium pressure altered the response to trigeminal nerve root stimulation in the same manner. The results are consistent with additive rather than antagonistic effects of pressure and a barbiturate on the determinants of output from the respiratory centre-motor neurone pathway. Pressure-anaesthetic antagonism may be a property unique to the neural circuitry which underlies awake behaviour and pressure-induced seizures, rather than reflecting a fundamental molecular-level antagonism.

Action Potentials↗
PubMed1991

Anesthetic effects on resting membrane potential are voltage-dependent and agent-specific.

Membrane hyperpolarization (increase in resting potential) together with a conductance increase has been suggested as a common mechanism of anesthetic action. The current study compared the effects of halothane, enflurane, and isoflurane on resting membrane potential and conductance of hippocampal CA1 neurons in vitro. At 1 MAC, halothane produced significant (P less than 0.01) hyperpolarization (-2.8 +/- 1.3 mV, mean +/- SD) accompanied by a conductance increase (6.2 +/- 2.7%). Enflurane also produced a significant (P less than 0.001) hyperpolarization (-3.15 +/- 1.2 mV); however, this was accompanied by a conductance decrease (-4.5 +/- 1.5%). Isoflurane produced variable effects. Anesthetic-induced hyperpolarization was maximal in neurons with more negative initial resting potentials and was reduced by depolarization. Across agents, these relatively small changes in resting potential were not correlated with decreases in excitability as measured by synaptically evoked population spike depression. The results are not consistent with a common action of the three agents on a single ionic channel.

Anesthetics↗
PubMed1991

Isoflurane and an alpha 2-adrenoceptor agonist suppress nociceptive neurotransmission in neonatal rat spinal cord.

Analgesia is an important component of general anesthesia. alpha 2-adrenoceptor agonists such as clonidine and dexmedetomidine are effective analgesics at the spinal level, and furthermore, they reduce the volatile anesthetic requirement. In order to probe a possible spinal-level contribution to general anesthetic-induced analgesia, the effects of dexmedetomidine were tested in an isolated spinal cord preparation. The effects of dexmedetomidine were compared with those of isoflurane, and dexmedetomidine-isoflurane interactions were explored. The test response was a nociceptive-related slow ventral root potential (slow VRP) recorded from the isolated neonatal rat spinal cord in response to electrical stimulation of a dorsal root. At 0.2-1.28 vol%, isoflurane reversibly depressed the slow VRP. At a lower concentration (0.14 vol%), isoflurane increased the slow VRP in three of five preparations. At 1.0-1.28 vol%, isoflurane also depressed the monosynaptic reflex. Recovery on washout usually was to a level greater than control. The N-methyl-D-aspartate (NMDA) receptor antagonist (DL)-2-amino 5-phosphonovalerate (10 microM) prevented the rebound to levels above control on isoflurane washout. The earlier components of the slow VRP were more sensitive to isoflurane than were the later. Dexmedetomidine (0.5-10 nM) depressed the slow VRP and had no effect on the monosynaptic reflex. The slow VRP depends on both substance P and glutamate NMDA-receptor-mediated neurotransmission; isoflurance and dexmedetomidine depressed responses to both substance P and NMDA. Although the two agents depress responses to the same neurotransmitters, there is no evidence that they act at the same cellular site(s). There was no significant interaction between dexmedetomidine and isoflurane. The results suggest that isoflurane exerts marked inhibitory effects on spinal neurotransmission, depressing both substance P and glutamate-mediated pathways. There is a possible biphasic effect on the NMDA receptor. To the extent that nociception depends on these neurotransmitters, isoflurane may be expected to exert profound analgesic effects at the spinal level. By blocking responses to strongly arousing stimuli, these effects may contribute to general anesthesia. Suppression of nociceptive neurotransmission at the spinal level may contribute to dexmedetomidine's anesthetic-sparing properties as well as to analgesia by this agent.

Adrenergic alpha-Agonists↗
PubMed1990

Evidence for reduced presynaptic Ca2+ entry in a lobster neuromuscular junction at high pressure.

1. Previous studies have shown that hyperbaric pressure depresses synaptic transmission and have suggested that the effect is primarily on transmitter release. The present study analysed the effects of pressure at a crustacean neuromuscular junction. Changes in pressure were compared to changes in extracellular calcium concentration [Ca2+]o with respect to effects on excitatory junction potential (EJP) amplitude, time course, facilitation and potentiation. 2. The effects of 10.1 MPa pressure on EJP amplitude, facilitation and potentiation, but not time course, were mimicked by reducing [Ca2+]o to approximately one-half the normal level. 3. The effects of pressure and the interaction between compression and calcium concentration were analysed in terms of a model of transmitter release. The model assumes that release is dependent on internal calcium concentration, as modulated by both influx and removal processes; that calcium influx is a saturating function of [Ca2+]o; and that release and removal are saturating functions of [Ca2+]i. 4. The results were consistent with the hypothesis that increased pressure acts primarily to reduce calcium influx into the nerve terminal.

Animals↗
PubMed1989

General anaesthetic modification of synaptic facilitation and long-term potentiation in hippocampus.

The synaptic integrative properties of facilitation and potentiation are important determinants of cortical neurone excitability. The present study measured the effects of halothane and methoxyflurane on synaptic facilitation, paired-pulse potentiation, and long-term potentiation (LTP) in CA1 pyramidal neurones of rat hippocampal slices. Methoxyflurane 0.16vol% and halothane 1.2 vol% depressed population spike amplitudes by approximately 100%, but halothane did so with relatively little (less than 10%) depressant effect on the field excitatory postsynaptic potential (EPSP). Both agents enhanced EPSP facilitation, halothane more than methoxyflurane. Halothane consistently enhanced paired-pulse population spike potentiation; methoxyflurane sometimes diminished it. Halothane reduced the probability of LTP induction to an extent correlated with block of population spike responses in the inducing stimulus train (r = 0.92); methoxyflurane did not block LTP. The results suggest that these agents affect cortical excitability by multiple actions, the distribution of actions being specific to each agent.

Animals↗