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At least 19 recordsLinked to original sources
PubMed1992

Comparison of binding at strychnine-sensitive (inhibitory glycine receptor) and strychnine-insensitive (N-methyl-D-aspartate receptor) glycine binding sites.

We compared, for a number of ligands to the two receptors, the displacement of [3H]strychnine binding to the glycine-gated chloride channel of spinal cord and brainstem synaptic membranes to the displacement of [3H]glycine binding to the NMDA receptor complex of hippocampal and cortex synaptic membranes. Glycine and beta-alanine are recognized by both receptors. In the NMDA receptor glycine antagonists, the kynurenic acids, most of the quinoxalinediones, and the (R)-enantiomer of HA-966 had little affinity at the strychnine-sensitive site. Surprisingly, the quinoxalinedione widely used as an AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor antagonist, NBQX (2,3-dihydro-6-nitro-sulfamoylbenzo[f]quinoxaline-2,3-dione) displaced [3H]strychnine binding (IC50 = 11 microM) and to a lesser extent [3H]glycine binding (IC50 = 119 microM). Of the compounds tested, only strychnine, brucine, taurine and (S)-HA-966 were more potent displacers of [3H]strychnine than of glycine binding. Generally, the two glycine recognition sites appear to have remarkably different structural requirements.

Animals↗
PubMed1977

The binding of strychnine and strychnine analogs to synaptic membranes of rat brainstem and spinal cord.

Crude synaptic membranes were isolated from rat pons, medulla and spinal cord by differential centrifugation. The specific binding of [3H]strychnine, obtained by subtracting from the bound radioactivity the amount not displaced by 50 micronm unlabeled strychnine, was saturable with a KD value of 12 nM. The dissociation constants (KD values) for the binding of several strychnine analogs to the strychnine site in vitro were determined and found to be highly correlated with the convulsant and lethal effects in the mouse. However, neither the biological activities in the mouse nor the binding activity in vitro correlated with the n-octanol-water distribution coefficients. The results are in accord with the concept that the [3H]strychnine binding site detected in vitro is the site of pharmacological activity in vivo.

Animals↗
PubMed1975

Ontogeny of behavioral sensitivity to strychnine in the chick embryo: evidence for the early onset of CNS inhibition.

The development of behavioral sensitivity to strychnine has been studied in the chick embryo between day 7 of incubation and 1 day posthatching. The earliest response to systemically applied strychnine was a marked depression of spontaneous motility at high concentrations of the drug. Lower concentrations had no effect at this time (6-7 days). About 2 days later, on day 81/2 or 9, strychnine induced a statistically reliable increase in spontaneous motility (hyperactivity). This consisted of a brief (i.e. 1-2 min) excitatory response which was followed by a return to baseline activity levels in the case of low drug concentrations, or a depression of activity in the case of low drug concentrations, or a depression of activity in the case of higher concentrations. By 11 days of incubation the brief excitatory response following strychnine had increased in duration to about 4 min. This was also the case for 13-day embryos. At no time between 7 and 13 days were convulsions produced by strychnine, even at concentrations several times greater than that required to induce hyperactivity. For the first time at 16 days myoclonic convulsions were observed following strychnine. These usually began soon after the initial hyperactivity and frequently lasted for as long as 30 min. At the same time the sensitivity of the embryo to strychnine increased, compared to earlier stages. By 18 days strychnine most often induced an immediate convulsive response without the preceding brief hyperactivity. This was also typical of newly hatched chicks. The systemic application of glycine at 9 and 13 days of incubation produced a slight, but statistically reliable, depression of ongoing spontaneous motility, consistent with what one might expect if glycine were acting as an inhibitory neurotransmitter. It typically took between 3 and 4 min following injection for this glycine response to occur. Biochemical, electrophysiological and neuroanatomical evidence was reviewed in an attempt to support the suggestion that the strychnine and glycine data summarized above may reflect the presence of strychnine-sensitive postsynaptic inhibitory processes in the chick spinal cord. Additionally, comparative data on the relative onset of excitatory and inhibitory processes in the developing spinal cord were discussed. It was concluded that, although the data are still imcomplete concerning the question of whether, developmentally, inhibition is a primary or secondary acquisition, inhibitory mechanisms nevertheless appear rather early during vertebrate neurogenesis.

Animals↗
PubMed1991

Site-selective oxidation of strychnine by phenobarbital inducible cytochrome P-450.

The metabolism of strychnine was studied using liver microsomes of rats treated with phenobarbital or 3-methylcholanthrene (MC). The phenobarbital-treatment resulted in 7.9-fold and 4.8-fold increases in 2-hydroxylation and N-oxidation of strychnine, respectively. The formation of 16-hydroxystrychnine, strychnine 21,22-epoxide and 22-hydroxystrychnine was induced about 2-fold. MC-treatment resulted in only 1.4-fold induction of each oxidation activity. In addition, strychnine 2-hydroxylation activity was markedly induced in liver microsomes of phenobarbital-treated mice, guinea pigs, rabbits and dogs (2.5-10.5-fold). Induction of N-oxidation activity was also higher than that of the three other oxidation activities. A reconstituted system of strychnine metabolism using cytochrome P-450 isozymes, P-450I (P450IIB1) and P-450II (P450IIB2), purified from liver microsomes of phenobarbital-treated rats showed significantly high and selective activities towards 2-hydroxylation and N-oxidation of strychnine. This characteristic metabolism of strychnine appears to occur in common with interspecies P450IIB gene subfamily. The pH Optima of 2-hydroxylation and N-oxidation of strychnine were between 8.4 and 8.6 in the microsomes of phenobarbital-treated rats, while that of N-demethylation of benzphetamine, a typical substrate of phenobarbital-inducible cytochrome P-450, was between 7.4 and 7.6. In a reconstituted system with P-450I, strychnine oxidation was little affected by pH change, while benzphetamine N-demethylation activity was decreased in the alkaline side. Among several oxidations tested, only ethylmorphine N-demethylation underwent the same pH effect as did strychnine oxidation with the microsomes and reconstituted system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

MDL 27,531 selectively reverses strychnine-induced seizures in mice.

1. Strychnine-sensitive glycine receptors are primarily localized in the brainstem and spinal cord where they are the major mediators of postsynaptic inhibition. A compound which acts functionally like a glycine receptor agonist would be potentially useful as a pharmacological tool and as a therapeutic agent for treating disorders of glycinergic transmission. 2. MDL 27,531 (4-methyl-3-methylsulphonyl-5-phenyl-4H-1,2,4-triazole) blocked strychnine-induced tonic extensor seizures in mice following either intraperitoneal (ED50 = 12.8 mg kg-1; 30 min) or oral (ED50 = 7.3 mg kg-1; 30 min) administration. Time course studies revealed a maximal effect at 30-60 min, though significant activity was still seen after 24 h. 3. MDL 27,531 was selective in antagonizing strychnine seizures and little or no activity was seen against seizures produced by other chemical convulsants (bicuculline; quinolinic acid; mercaptopropionic acid); by electrical stimuli (maximal electroshock); or by sensory stimuli (audiogenic seizure susceptible mice). MDL 27,531 blocked pentylenetetrazol-induced seizures with an ED50 = 55 mg kg-1. This profile differed from those of the anticonvulsants diazepam, valproic acid, and diphenylhydantoin. 4. The antagonism of strychnine seizures by MDL 27,531 occurred at doses that did not produce signs of sedation (suppression of spontaneous motor activity), motor ataxia (disruption of rotarod performance), muscle relaxation (inhibition of morphine-induced Straub tail), or CNS depression (potentiation of hexobarbitone sleep time). MDL 27,531 had less side effect potential (as derived from ratios obtained from the above measures) relative to those of the known muscle relaxants diazepam and baclofen. 5. Although MDL 27,531 behaved functionally like a selective agonist at the strychnine-sensitive glycine receptor, the compound did not alter the in vitro binding of [3H]-strychnine to mice brainstem/spinal cord membranes at concentrations of up to 100 microM. In further in vitro binding assays, MDL 27,531 at concentrations of up to 100 microM, did not displace the binding of [3H]-muscimol, [3H]-flunitrazepam, or["S]-t-butylbicyclophosphorthionate to rat cortical membranes. These ligands bind to the 7y-aminobutyric acid (GABA), benzodiazepine, and picrotoxin-convulsant binding sites, respectively.6. MDL 27,531 (10-100mgkg-', i.p.) enhanced binding of the benzodiazepine antagonist [3H]-Ro15-1788 to mouse cerebral cortex in vivo without directly affecting GABA levels.7. Ro 15-1788 (16, 32 mg kg-') significantly blocked the MDL 27,531 antagonism of strychnineinduced seizures, though this antagonism was not competitive. The same doses of Ro 15-1788 produced parallel rightward shifts in the dose-response curves for diazepam inhibition of pentylenetetrazol-induced seizures, consistent with a competitive antagonism.8. Thus, MDL 27,531 acts functionally like an agonist at the strychnine-sensitive glycine receptor in its capacity to reverse selectively strychnine-induced seizures. Though the precise mechanism of action of MDL 27,531 is unknown, MDL 27,531 may act at an allosteric site on the strychnine-sensitive receptor which produces agonist-like activity.

Administration, Oral↗
PubMed1990

Localization of the strychnine binding site on the 48-kilodalton subunit of the glycine receptor.

Amino acid residues that participate in antagonist binding to the strychnine-sensitive glycine receptor (GlyR) have been identified by selectively modifying functional groups with chemical reagents. Moreover, a region directly involved with strychnine binding has been localized in the 48-kDa subunit of this receptor by covalent labeling and proteolytic mapping. Modification of tyrosyl or arginyl residues promotes a marked decrease of specific [3H]strychnine binding either to rat spinal cord plasma membranes or to the purified GlyR incorporated into phospholipid vesicles. Occupancy of the receptor by strychnine, but not by glycine, completely protects from the inhibition caused by chemical reagents. Furthermore, these tyrosine- or arginine-specific reagents decrease the number of binding sites (Bmax) for [3H]strychnine binding without affecting the affinity for the ligand (Kd). These observations strongly suggest that such residues are present at, or very close to, the antagonist binding site. In order to localize the strychnine binding domain within the GlyR, purified and reconstituted receptor preparations were photoaffinity labeled with [3H]strychnine. The radiolabeled 48-kDa subunit was then digested with specific chemical proteolytic reagents, and the peptides containing the covalently bound radioligand were identified by fluorography after gel electrophoresis. N-Chlorosuccinimide treatment of [3H]strychnine-labeled 48K polypeptide yielded a single labeled peptide of Mr approximately 7300, and cyanogen bromide gave a labeled peptide of Mr 6200.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

The effects of spinal gray activation by strychnine on the motor evoked potential in the rat.

Spinal motor evoked potentials were elicited by electrical stimulation of the motor cortex in 14 rats before and after the application of strychnine to the surface of the spinal cord. Strychnine applied to the high cervical cord resulted in the emergence of additional peaks at the site of application and in electrodes positioned distally on the middle and lower thoracic cord. The strychnine-induced peaks occurred earlier and were larger in amplitude (P less than 0.01) in the distal spinal cord. Strychnine applied to the lower thoracic cord resulted in similar peak generation in the lower thoracic cord and in the spinal cord proximal to the application of strychnine. These findings demonstrate that strychnine-induced motor evoked potential changes arise from spinal gray activity induced by efferent pathways activated during transcortical stimulation. The role of the propriospinal tract in mediating the distal effects of strychnine is discussed. In conclusion, the strychnine-induced peaks of the motor evoked potential may be used as a measure of spinal gray integrity in experimental spinal cord injury models.

Animals↗
PubMed1992

The neurotoxicants strychnine and bicuculline protect renal proximal tubules from mitochondrial inhibitor-induced cell death.

Glycine-induced cytoprotection of renal proximal tubules exposed to chemical- or hypoxic/anoxic-induced cell death is shared by a few amino acid agonists of the neuronal strychnine-sensitive glycine receptor. The goal of this study was to determine if antagonists of the strychnine-sensitive glycine receptor attenuated the cytoprotective effects of glycine. Strychnine did not antagonize the cytoprotective effects of glycine in proximal tubules exposed to antimycin A. In contrast, strychnine was cytoprotective, was equipotent as glycine (EC50 = 0.4 mM), and the combination of strychnine and glycine was additive. Likewise, bicuculline and norharmane were cytoprotective but 20-50% less potent than glycine. These results suggest that glycine and strychnine act as a common site to produce proximal tubule cytoprotection, but this site does not share the same potency and agonist/antagonist properties as the neuronal strychnine-sensitive glycine receptor.

Animals↗
PubMed1979

Block of sodium conductance and gating current in squid giant axons poisoned with quaternary strychnine.

Quaternary strychnine blocks sodium channels from the axoplasmic side, probably by insertion into the inner channel mouth. Block is strongly voltage dependent, being more pronounced in depolarized than in resting axons. Using potential steps as a means to modulate the level of block, we investigate strychnine effects on sodium and gating currents at +50 and -50 mV. We analyze our data in terms of the simplest possible model, wherein only an open channel may receive and retain a strychnine molecule. Our main findings are (a) block by strychnine and inactivation resemble each other and (b) block of sodium and gating currents by strychnine happen with closely similar time-courses. Our data support the hypothesis of Armstrong and Bezanilla (1977) wherein an endogenous blocking particle causes inactivation by inserting itself into the inner mouth of the sodium channel. Quaternary strychnine may act as an artificial substitute for the hypothetical endogenous blocking particle. Further, we suggest that at least 90% of the rapid asymmetrical displacement current in squid axons is sodium channel gating current, inasmuch as quaternary strychnine can block 90% of the displacement current simultaneously with sodium current.

Animals↗
PubMed1990

Strychnine protection against excitotoxic cell death in primary cultures of rat cerebral cortex.

Strychnine-insensitive glycine receptors are known to modulate the toxicity of excitatory amino acids via an allosteric action at the N-methyl-D-aspartate receptor complex. To elucidate whether strychnine-sensitive glycine receptors may also influence excitotoxicity, the effect of strychnine on the excitotoxic cell death was examined in primary cultures of the rat cerebral cortex. To exclude any interference at the N-methyl-D-aspartate receptor complex, cell death was evoked by kainic acid. The release of lactic dehydrogenase (LDH) into the culture medium was taken as a quantitative measure of cell death. Strychnine reduced the excitotoxic cell death in a concentration-dependent fashion. This finding indicates that glycine may modulate the vulnerability of cortical cells to excitotoxic insults not only via the strychnine-insensitive population of glycine receptors within the N-methyl-D-aspartate receptor-complex, but also via strychnine-sensitive receptor channels.

Animals↗
PubMed1990

Characterization and regional distribution of strychnine-insensitive [3H]glycine binding sites in rat brain by quantitative receptor autoradiography.

Recent evidence suggests that a strychnine-insensitive glycine modulatory site is associated with the N-methyl-D-aspartate receptor-channel complex. A quantitative autoradiographic method was used to characterize the pharmacological specificity and anatomical distribution of strychnine-insensitive [3H]glycine binding sites in rat brain. [3H]Glycine binding was specific, saturable, reversible, pH and temperature-sensitive and of high affinity. [3H]Glycine interacted with a single population of sites having a KD of approximately 200 nM and a maximum density of 6.2 pmol/mg protein (stratum radiatum, CA1). Binding exhibited a pharmacological profile similar to the physiologically defined strychnine-insensitive glycine modulatory site. Binding was stereoselective; the rank order of potency of simple amino acids as displacers of binding was: glycine greater than D-serine greater than D-alanine greater than L-serine greater than L-alanine greater than L-valine greater than D-valine. Binding was not altered by the inhibitory glycine receptor ligand, strychnine, by the glutamate agonists, quisqualate and kainate, or by GABA receptor selective ligands. Most competitive agonists or antagonists of the N-methyl-D-aspartate recognition site were ineffective displacers of glycine binding. The exceptions were the aminophosphono series of antagonists, D-alpha-aminoadipate, gamma-D-glutamyglycine and beta-D-aspartylaminomethylphosphonic acid. However, the inhibition of [3H]glycine binding produced by the aminophosphono compounds could be accounted for by the level of glycine contamination present in these compounds. The non-competitive NMDA receptor-channel blockers, phencyclidine, its thienyl derivative, and MK-801 did not alter glycine binding. Kynurenate, glycine methylester, L-serine-O-sulfate, L-homocysteic acid, and several glycine-containing dipeptides were effective displacers of glycine binding. Structure-activity relations of agonists and antagonists of the strychinine-insensitive glycine binding site are discussed. The distribution of strychnine-insensitive [3H]glycine binding was heterogeneous with the following rank order of binding densities: hippocampus greater than cerebral cortex greater than caudate-putamen greater than or equal to thalamus greater than cerebellum greater than brain stem. This distribution of binding was correlated with N-methyl-D-aspartate-sensitive [3H]glutamate binding (r2 = 0.77; P less than 0.001; Pearson product-moment) and [3H]thienylcyclohexylpiperidine binding (r2 = 0.72; P less than 0.001). These observations are consistent with the hypothesis that the strychnine-insensitive glycine binding site is closely associated with the N-methyl-D-aspartate receptor-channel complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Antagonism of ligand-gated ion channel receptors: two domains of the glycine receptor alpha subunit form the strychnine-binding site.

The inhibitory glycine receptor (GlyR) is a member of the ligand-gated ion channel receptor superfamily. Glycine activation of the receptor is antagonized by the convulsant alkaloid strychnine. Using in vitro mutagenesis and functional analysis of the cDNA encoding the alpha 1 subunit of the human GlyR, we have identified several amino acid residues that form the strychnine-binding site. These residues were identified by transient expression of mutated cDNAs in mammalian (293) cells and examination of resultant [3H]strychnine binding, glycine displacement of [3H]strychnine, and electrophysiological responses to the application of glycine and strychnine. This mutational analysis revealed that residues from two separate domains within the alpha 1 subunit form the binding site for the antagonist strychnine. The first domain includes the amino acid residues Gly-160 and Tyr-161, and the second domain includes the residues Lys-200 and Tyr-202. These results, combined with analyses of other ligand-gated ion channel receptors, suggest a conserved tertiary structure and a common mechanism for antagonism in this receptor superfamily.

Amino Acid Sequence↗
PubMed1977

Effects of strychnine on the potassium conductance of the frog node of Ranvier.

The nature of the block of potassium conductance by strychnine in frog node of Ranvier was investigated. The block is voltage-dependent and reaches a steady level with a relaxation time of 1 to several ms. Block is increased by depolarization or a reduction in [K+]O as well as by increasing strychnine concentration. A quaternary derivative of strychnine produces a similar block only when applied intracellularly. In general and in detail, strychnine block resembles that produced by intracellular application of the substituted tetraethylammonium compounds extensively studied by C.M. Armstrong (1969. J. Gen Physiol. 54:553-575. 1971. J. Gen. Physiol. 58:413-437). The kinetics, voltage dependence, and dependence on [K+]O of strychnine block are of the same form. It is concluded that tertiary strychnine must cross the axon membrane and block from the axoplasmic side in the same fashion as these quaternary amines.

Action Potentials↗
PubMed1978

Effect of intraventricular administration of anti-somatostatin gamma-globulin on the lethal dose-50 of strychnine and pentobarbital in rats.

Effects of intraventricular injection of sheep anti-somatostatin gamma-globulin (anti-SSG) on strychnine-induced seizures, strychnine LD50, and pentobarbital LD50 were examined in male rats under light ether anesthesia. Ten microliters of anti-SSG given 2 h earlier significantly decreased the duration of strychnine-induced seizures as compared with that in the control rats pretreated with normal sheep gamma-globulin (NSG). This effect of anti-SSG seemed to be specific, as there was no difference in seizure duration between sheep anti-LHRH gamma-globulin (anti-LHRHG)- and NSG-pretreated rats. Survival rates in anti-SSG-pretreated rats after injection of strychnine and pentobarbital were significantly larger (P less than 0.01 and P less than 0.05, respectively) than those in the control rats receiving NSG. The administration of anti-SSG resulted in 26.7% and 22.9% increases in the LD50 of strychnine and pentobarbital, respectively. These results indicate that endogenous somatostatin in the cerebrospinal fluids and/or the periventricular tissue nodulates the response of the central nervous system to strychnine and pentobarbital in rats.

Animals↗
PubMed1976

Spontaneous bioelectric activity of cultured Purkinje cells during exposure to glutamate, glycine, and strychnine.

The addition of glutamate to the bathing medium increased the average firing rate of cerebellar rat Purkinje cells in vitro. At concentrations lower than 10(-6) M, there was no deviation from controls in the firing pattern or rate that was detectable. At 10(-3) M glutamate, the amplitude of the action potentials was gradually decreased until all activity was abolished. The action of glutamate was rapid in onset and reversible. Glycine produced sustained depression of firing at concentrations higher than 10(-3) M. This inhibition was strychnine-insensitive and considered nonspecific. Strychnine, on the other hand, exerted an excitatory influence on Purkinje cells when applied at low concentrations (10(-8) TO 10(-6) M). The firing became more irregular and complex discharges appeared. Higher concentrations of strychnine (greater than 10(-5) M) inhibited the spontaneous activity. The effect of strychnine was partly reversible. The data suggest that low concentrations of strychnine lower the threshold for inputs at excitatory as well as inhibitory synapses.

Action Potentials↗
PubMed1979

Some observations on habituation of the flexor reflex in the rat: the influence of strychnine, bicuculline, spinal transection, and decerebration.

The involvement of inhibition in habituation of the flexor reflex was investigated in intact, spinal, and decerebrate rats. Strychnine and bicuculline were administered in order to determine the contribution of certain forms of central inhibition to the development of habituation. Both strychnine and bicuculline reduced habituation in the intact rat but did not do so in the spinal preparation. Strychnine, in fact, caused a facilitation of habituation in the spinal rat. The impairment of habituation by strychnine was related to the intensity of stimulation used to elicit the reflex. Thus, the effect of strychnine was only demonstrable when relatively high intensities were used. Flexor reflex habituation was shown to be more pronounced in the decerebrate than in the spinal preparation. This difference could be demonstrated only when stimuli of high intensity were given. It is concluded that, in the absence of supraspinal influences, habituation of the flexor reflex does not require inhibitory mechanisms. However, inhibition may play a role in habituation of the component of the reflex that utilizes descending influences.

Animals↗
PubMed1979

Is the pressor response to strychnine centrally mediated?

Intravenous administration of strychnine (0.003-0.300 mg . kg-1) to curarized, chloralosed dogs induced hypertension and tachycardia. In spinal cord-transected dogs, intravenous administration of strychnine no longer elicited a rise in blood pressure and heart rate. Intracisternal injections of strychnine also produced hypertension and tachycardia but at lower doses. Similar results were obtained after intrathecal administration of strychnine in doses significantly different from those effective on intravenous and intracisternal administration. These findings suggest that the central nervous system may be involved in the haemodynamic changes induced by strychnine, but did not allow the site of action to be located.

Animals↗
PubMed1990

Glycine stimulates [3H]noradrenaline release by activating a strychnine-sensitive receptor present in rat hippocampus.

Rat hippocampus slices were prelabeled with [3H]noradrenaline ([3H]NA) and depolarized by superfusion with KCl. The release evoked by 12 mM K+ was totally calcium-dependent and more than 90% tetrodotoxin (TTX)-sensitive. Glycine (0.1-1 mM) increased the K(+)-evoked [3H]NA overflow in a concentration-dependent manner. The effect of 1 mM glycine reached 300%. Strychnine (0.3 microM) shifted to the right the concentration-response curve for glycine. The effect of glycine (0.1 or 1 mM) was totally abolished by 3 microM strychnine but was unaffected by the GABAA receptor antagonist, bicuculline (10 microM), or by 100 microM of 1-hydroxy-3-aminopyrrolidone-2 (HA-966), a proposed antagonist of glycine at the strychnine-insensitive site located on the N-methyl-D-aspartate (NMDA) receptor. The effect of glycine was mimicked by L-serine, although less potently; the release of [3H]NA was enhanced by 200% in presence of 3 mM L-serine. At this concentration D-serine was ineffective. Strychnine shifted to the right the concentration-response curve for L-serine. Glycine (1 mM) had only a minor effect (less than 20% potentiation) on the release of [3H]NA evoked by 12 mM KCl in hippocampal synaptosomes. While the effect of glycine in slices was increased by decreasing the depolarizing concentration of K+ (about 500% potentiation at 9 mM K+), the response of synaptosomes remained minimal, even in presence of 9 mM KCl. Hippocampal synaptosomes prelabeled with [3H]glycine released the radiolabeled amino acid when exposed to superfusion with 12 mM KCl. The release of [3H]glycine was more than 75% calcium-dependent. The results suggest that the release of NA in rat hippocampus may be enhanced by glycine through the activation of a strychnine-sensitive receptor. This receptor does not seem to be located on noradrenergic terminals.

Animals↗