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D O Carpenter

Publications and source records attributed to D O Carpenter.

At least 163 records · Page 9Linked to original sources
PubMed1984

N-Methyl-D-aspartate and L-aspartate activate distinct receptors in piriform cortex.

The effects of ionophoretically applied N-methyl-DL-aspartate (NMDA) and aspartate on identified pyramidal neurons in rat piriform cortex were examined in isolated, submerged, and perfused brain slices. NMDA was more potent than aspartate in eliciting neuronal discharge. Perfusion of the acidic amino acid antagonists, DL-2-amino-5-phosphonovalerate (APV), 10(-6) or 10(-5) M, DL-2-amino-7-phosphonoheptanoate (APH), 10(-5) M, and gamma-D-glutamylglycine (gamma DGG), 10(-5) M, selectively blocked the response to NMDA without effect on the response to aspartate. At higher concentrations which blocked responses to both NMDA and aspartate, gamma DGG blocked kainate responses and depressed glutamate and quisqualate responses. These results suggest that in piriform neurons NMDA and aspartate act at distinct receptor sites, not a common receptor site, and that both of these sites are distinct from those that mediate responses to glutamate, quisqualate, and kainate.

2-Amino-5-phosphonovalerate↗
PubMed1984

A study of the cholinolytic actions of strychnine using the technique of concentration jump relaxation analysis.

The blocking actions of strychnine on excitatory acetylcholine (ACh) responses in isolated, voltage clamped Aplysia neuronal cell bodies has been studied using a rapid drug application technique. Rapid microperfusion of strychnine (10-50 microM) produced a reduction of the steady-state ACh-induced inward current in Aplysia neurons which decayed exponentially with a highly dose-dependent time constant. At the cessation of strychnine perfusion the ACh-induced current recovered to its original value with an exponential time course which was not sensitive to the dose of strychnine previously applied. The calculated association (k1) and dissociation (k-1) constants for a pseudo-first-order reaction between strychnine and its binding site were k1 = 1.2 X 10(4) M-1. sec-1 and k-1 = 0.12 sec-1 (KD = 1 X 10(-5) M-1). These results demonstrate that concentration jump relaxation experiments can be performed on isolated neurons for the study of voltage-independent antagonists by the use of rapid microperfusion systems and provide the first direct estimates to date of the rate constants of the cholinolytic effect of strychnine.

Animals↗
PubMed1984

Peptide-induced emesis in dogs.

Systemic administration of apomorphine, angiotensin II, neurotensin and leucine-enkephalin induces emesis in dogs in a dose-dependent fashion. Receptors for Leu-enkephalin and angiotensin II but not apomorphine show receptor desensitization, such that a second systemic administration 5 min after the first is ineffective. Domperidone blocked the emetic response to apomorphine but not to Leu-enkephalin or angiotensin II. Naloxone selectively blocked the Leu-enkephalin response, while saralasin blocked responses to both angiotensin II and Leu-enkephalin, but not apomorphine. Chlorpromazine prevented the emetic response to all agents, suggesting a dopamine receptor in the emetic pathway on the brain side of the blood-brain barrier. In dogs with ablation of the area postrema the emetic response to apomorphine and all peptides was prevented.

Angiotensin II↗
PubMed1984

Behavioral and electrophysiological studies of peptide-induced emesis in dogs.

The electrophysiological responses of neurons in the canine area postrema (AP) to ionophoretic application of neuropeptides and transmitters were studied and correlated with the presence or absence of an emetic response on systemic administration. Of 17 common neuropeptides 11 were emetic when applied systemically at doses of 0.03-0.35 mg/kg. The emesis was dose dependent and was no longer observed in animals with chronic ablation of the AP. The responses of 122 AP single units were recorded. Neurons were silent at rest, and most were excited by glutamate, apomorphine, and dopamine. Excitatory responses to each of eight emetic peptides were recorded in 22-65% of cells studied; no responses were found to two peptides that were not emetic. The response to glutamate was always a brief, high-frequency discharge; the responses to all 13 other excitatory substances were of long latency, low frequency, and long duration. With high ionophoretic current or multiple applications, units would frequently become spontaneously active for many minutes or longer. The similarity of response of so many substances on small neurons suggests a common ionic or metabolic mechanism underlying the response. The direct correlation between the occurrence of emesis on systemic administration and the presence of excitatory receptors on AP neurons provides strong support for the proposed role of the AP as the chemoreceptor trigger zone for emesis.

Action Potentials↗
PubMed1983

Vipoxin both activates and antagonizes three types of acetylcholine response in Aplysia neurons.

The effects of vipoxin, a 13,000 Dalton protein component of Russell's viper venom on responses of voltage-clamped Aplysia neurons to acetylcholine (ACh) and monoamines has been studied. At low doses vipoxin reversibly antagonizes all 3 types of ionic response to ACh or carbachol, the order of susceptibility to blockade being Na+ greater than K+ greater than Cl-. High doses of vipoxin directly evoke the same ionic response on a given cell as that evoked by ACh. Responses to vipoxin are reversibly antagonized by cholinergic antagonists (e.g. hexamethonium, tetraethylammonium), but not by monoamine antagonists (e.g. bufotenine, ergometrine, cimetidine). In addition to activation of cholinergic responses, high doses of vipoxin also produce a reversible potentiation of responses to dopamine and 5-hydroxytryptamine on some cells. In contrast to its effects on Aplysia neurons, vipoxin has neither agonist nor antagonist actions at the frog neuromuscular junction. These results suggest that this venom protein acts as a partial agonist at molluscan ACh receptors and provides evidence for some phylogenetic difference between molluscan and vertebrate ACh receptors.

Acetylcholine↗
PubMed1983

Two-component desensitization of three types of responses of acetylcholine in Aplysia.

Both the onset of and recovery from desensitization of three types of responses to acetylcholine in Aplysia californica occurred by biphasic kinetics. The fast component of onset recovered at a slower rate than the slow component of onset. The rates of onset and recovery were widely different when the three response types were compared. These data suggest that receptor properties determine two components in the desensitization process that are similar for all three responses, while the channel determines the rates of these processes.

Acetylcholine↗
PubMed1983

Choroidal blood flow. III. Reflexive control in human eyes.

Choroidal blood flow helps maintain a stable temperature environment for the outer retinal layers, especially in the macular area. Recent studies in monkeys have demonstrated a centrally mediated reflexive mechanism that increases choroidal blood flow in response to light or light-generated heat. This increase in choroidal blood flow can be detected as an elevation in ocular surface temperature. With the use of ocular surface temperature as a semiquantitative index of alterations in choroidal blood flow, the existence of a similar reflex was demonstrated in normal human volunteers.

Blood Circulation↗
PubMed1983

Kinetics of acetylcholine-activated cation channel blockade by the calcium antagonist D-600 in Aplysia neurons.

The effects of the calcium channel blocker D-600 on the cation channels activated by acetylcholine (ACh) was studied in voltage-clamped Aplysia neurons by voltage-jump relaxation analysis. D-600 blocked the steady-state ACh current in a highly voltage-dependent manner, the degree of antagonism increasing with membrane hyperpolarization. In the presence of D-600 the current relaxations following hyperpolarizing command steps became biphasic. The time constants of ACh-induced current relaxations (tau f), which approximate the mean channel lifetime, were reduced in a voltage-dependent manner, the degree of reduction of tau f increasing with increasing membrane potential. In addition to the acceleration of tau f, a slow, inverse kinetic component (tau s) of the relaxation appeared in the presence of D-600. The rate of this inverse kinetic component was accelerated either by increasing the agonist or antagonist dose or by increasing the membrane potential. These results suggest that D-600 acts to antagonize the acetylcholine response through a blockade of the open state of the transmitter-activated cation channel. Possible kinetic schemes for this interaction are discussed.

Acetylcholine↗
PubMed1983

Responses of neurons of canine area postrema to neurotransmitters and peptides.

The responses of 122 neurons in the area postrema of anesthetized dogs to 17 common transmitters and peptides were determined. Recordings were made from one barrel of a seven-barrel ionophoretic electrode. All neurons were silent at rest, but most could be detected and excited by the application of glutamate. The glutamate response was a brief, high-frequency response of less than 1-sec duration. Excitatory responses were also found to histamine, norepinephrine, serotonin, dopamine, apomorphine, angiotensin II, neurotensin, leucine enkephalin, vasoactive intestinal polypeptide, thyrotropin releasing hormone, gastrin, vasopressin, and substance P. While most neurons tested were excited by dopamine and apomorphine, approximately half of those studied were also excited by each of the other substances. Inhibitory responses were found to norepinephrine (6 of 15 cells) and histamine (3 of 45 cells). No responses were found to acetylcholine, somatostatin, or cholecystokinin. The responses to all 13 excitatory substances other than glutamate were similar. Typically these responses had a latency of 2-20 sec and lasted for 30 sec to 5 min on their first application. The frequency of discharge was usually low (approximately 0.5 Hz). Multiple applications of these agents often induced a maintained spontaneous discharge of low frequency. Each application also induced a transient incremental discharge at a frequency that rarely exceeded 2 Hz. The area postrema has been proposed to be the "chemoreceptor trigger zone" for emesis (Borison and Wang, 1953). All of the agents which excite area postrema neurons, with the exception of serotonin and norepinephrine, are emetic, while none of the three agents without excitatory effects is known to be emetic. Thus these results provide strong support for the central role of the area postrema in emesis. The similarity of response to so many substances on small neurons suggests a common ionic and/or metabolic mechanism underlying the response. The prolonged nature of the response to brief administration of these agents would seem to be appropriate for neurons which subserve a sensation and behavior such as nausea and vomiting.

Action Potentials↗
PubMed1983

Asymmetric distribution of acetylcholine receptors and M channels on prepyriform neurons.

The responses of pyramidal neurons of rat prepyriform cortex to ionophoretic application of acetylcholine (ACh) were studied in a submerged, perfused brain slice. ACh excited some neurons but only if applied to an area near to the cut surface of the slice. This area contained the basal dendrites of the pyramidal cells and some cell bodies. No excitation was seen if ACh was applied at depths of 250 microns or more from the cut surface, an area which contained only apical dendrites, although the apical dendrites were very sensitive to excitatory amino acids such as aspartate (Asp) and glutamate (Glu). On all neurons which did not discharge to ionophoretic application of ACh, ACh potentiated the response to Glu and Asp. No potentiation of amino acid responses was obtained on apical dendrites. The potentiation had a time course similar to that of the discharge of neurons which fired to ACh. This observation suggests that pyramidal neurons have receptors for ACh on basal but not apical dendrites. The ACh response in the basal dendrite-soma region was elicted by pilocarpine and blocked by atropine but not curare. This was true whether the response studied was direct excitation or potentiation of the response to an amino acid. The ACh response was associated with a voltage-dependent increase in membrane resistance which had a slow time course and appeared to be due to a turning off of an M current, as described by Brown and Adams (1980) in sympathetic ganglion cells. The effects of ACh were minimal at the resting potential but increased with depolartization. ACh had no effect on the current-voltage relation of the cell, except at depolarized potentials of less than -60 mV. Ionophoretic application of Ba2+ to the basal dendritic region resulted in potentiation of the amino acid responses and sometimes induced a discharge similar to that of ACh. Since Ba2+ mimics the ACh response, presumably by a direct blockade of the M channel, the effects of Ba2+ on apical dendrites were tested to determine whether these dendrites contain M channels associated with a transmitter receptor other than ACh. However, Ba2+ did not induce potentiation in apical dendrites, suggesting that M channels are also restricted to the basal dendrites or cell bodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1983

Apparent discrepancy between single-unit activity and [14C]deoxyglucose labeling in optic tectum of the rattlesnake.

Autoradiographic analysis of [1-14C]2-deoxy-D-glucose-6-phosphate ([14C]2-DG-P) accumulation in the rattlesnake brain stem and optic tectum was used in an effort to map infrared and visual neuronal pathways. Visual stimulation with a standard stimulus (a heat lamp) resulted in dense labeling of the superficial layers of the optic tectum. Infrared stimulation with the same standard stimulus resulted in labeling at the first synaptic relay, the lateral descending nucleus of the trigeminal tract (LDN-V), but not at higher levels, including the optic tectum. Systematic comparison of electrophysiological properties of tectal neurons was performed using the standard stimulus. Responses of infrared units in one hemitectum and visual units in the other, elicited by the same stimulus used in the [14C]2-DG-P experiments, were analyzed. There were no clear differences in the number, maximal density, spread, or rates of accommodation of visual units and infrared units, although the locus of maximal density was more superficial for visual units. In general, infrared units generated a greater number of action potentials than did visual units. All infrared units responded only to onset of the stimulus but they varied greatly in their ability to maintain discharge for the full duration of the stimulus. Most visual units exhibited on-, off-, or on-off responses. Four units showed only inhibition of spontaneous activity during the visual stimulation. There were significant differences in the evoked responses elicited by visual and infrared stimulation in response to the standard stimulus. Infrared stimuli generated single, large, triphasic on-responses, whereas visual stimulation generated complex multiphasic and long-lasting on- and off-responses. The major infrared on peak reached maximal amplitude at greater depths and was larger than the major visual on peak. Amplitude of the infrared peak fell off more rapidly with distance from the locus of its maximum than did amplitude of the visual peak. These observations are consistent with the view that infrared stimulation is effective in discharging neurons but is not associated with intense synaptic excitation. In contrast, visual stimulation apparently does produce intense synaptic activity, as suggested by the duration, complexity, and spread of the visual evoked response. Failure of this synaptic activity to produce more spikes in visual units probably reflects either depolarizing spike inactivation or the admixture of excitatory and inhibitory actions. Our observations suggest that 2-deoxy-D-glucose uptake is not necessarily correlated with the degree of action potential activation of specific neuronal pathways. The amount of [14C]2-DG-P labeling may reflect the metabolic requirements for support of synaptic depolarization as well as that supporting action potentials.

Animals↗
PubMed1982

Choroidal blood flow. I. Ocular tissue temperature as a measure of flow.

Temperature measurements were taken from the retina-choroid, scleral surface, or bulbar conjunctiva in cats and monkeys. Decreasing choroidal blood flow by elevating intraocular pressure produced a decrease in ocular tissue temperature. Confirmation of choroidal blood flow changes was obtained by the hydrogen washout technique, an independent measure of blood flow. We conclude that ocular tissue temperature can be used as a semiquantitative index of choroidal blood flow, and, being noninvasive, has potential clinical application.

Animals↗
PubMed1982

Choroidal blood flow II. Reflexive control in the monkey.

Temperature measurements were taken from (1) the retina-choroid in the macula, (2) the scleral surface, or (3) the bulbar conjunctiva of the cynomolgus monkey, while the fellow eye was exposed to a moderate-intensity light source. Light stimulation produced an increase in tissue temperature in the non-light-stimulated eye. The increase in tissue temperature presumably results from a reflexive increase in choroidal blood flow. Hydrogen washout measurements of blood flow in the retina-choroid confirmed this increase in flow. This active mechanism, along with the passive ability of the choroidal circulation to dissipate light-generated heat, may be an important physiologic safeguard in helping to maintain a stable temperature environment for the outer retinal layers in the macula.

Animals↗
PubMed1982

Dopamine produces muscle contractions and modulates motoneuron-induced contractions in Aplysia gill.

1. Dopamine has been reported to exist in unusually large quantities in Aplysia gill. The physiological role of this neurotransmitter in this organ was examined. 2. The addition of dopamine to a gill perfusate results in the contractions of the lateral and medial external pinnule muscles, the circular and longitudinal muscles of the afferent vessel, and the circular muscles of the efferent vessel. 3. Dopamine-induced contractions persist after chemical synaptic transmission is eliminated in the gill. This suggests that excitatory dopamine receptors are present on gill smooth muscle fibers themselves. 4. Dopamine also potentiates the gill response to action potentials in single identified gill motoneurons. Evidence presented suggests that muscle contractions and modulation of motoneuron contractions are independent phenomena. 5. While modulation may in part be mediated by increases in excitatory junction potential (EJP) amplitude, in many cases large increases in muscle contractions occur while the enhancement of EJPs is disproportionately small. 6. Dopamine's ability to produce muscle contractions suggests that there may be dopaminergic motoneuron innervation of the gill. We suggest that dopamine's modulatory actions may be mediated via modification of excitation-contraction coupling in smooth muscle fibers.

Animals↗
PubMed1982

The stabilizing effect of the choroidal circulation on the temperature environment of the macula.

A major physiologic function for the high-flow choroidal circulation is the stabilization of the temperature environment of the retina. This is especially important in the macular region, which lies at the focal point of the eye's optical system. Observations of temperature changes in the macula under varying conditions of ambient illumination and choroidal blood flow have established that the choroidal circulation serves a dual purpose in stabilizing retinal tissue temperature, acting both as a heat source and a heat sink, depending on prevailing tissue temperatures.

Animals↗
PubMed1982

Pharmacologic sensitivity of amino acid responses and synaptic activation of in vitro prepyriform neurons.

1. In an effort to identify the neurotransmitter released from terminals of the lateral olfactory tract (LOT) we have studied excitatory amino acid agonist and antagonist actions on population and single-unit responses in submerged and perfused slices of rat prepyriform cortex. Previous studies suggest that the transmitter at this synapse is either aspartate (Asp) or glutamate (Glu). 2. The field potential reflecting the monosynaptic activation of pyramidal neurons after stimulation of the LOT was reversibly depressed by bath perfusion of agonists, with an order of potency being kainic acid (KA) greater than N-methyl-DL-aspartate (NMDA) greater than homocysteic acid (HC) greater than Asp = Glu. 3. The synaptic field potential was essentially unaffected by DL-alpha-aminoadipic acid (AA), 2-amino-3-phosphonopropionic acid (APP), and DL-alpha-diaminopimelic acid (DAPA), all presumed to be selective for Asp receptors, and by L-glutamic acid diethyl ester (GDEE), presumed to be specific for Glu receptors. The field potential was depressed or abolished by 2-amino-4-phosphonobutyric acid (APB), an agent known to block Glu responses in insect muscle. 4. The effects of ionophoretic application of agonists were studied on single neurons recorded extracellularly. While there was some variability among neurons in relative agonist potency, all neurons were excited by the five agonists with relative potencies in general similar to those observed for the field potentials. 5. Responses to Glu and Asp were unaffected by AA, GDEE, and APB at concentrations up to 5 X 10(-3) M. Responses to KA, NMDA, and HC were often depressed by APB but were unaffected by the other antagonists. The excitation on stimulation of the LOT was consistently, rapidly, and reversibly blocked by APB. 6. These observations are not consistent with either Glu or Asp being the neurotransmitter of the LOT.

Animals↗