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K M Johnson

Publications and source records attributed to K M Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1994

(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) induces burst firing via an inositol-1,4,5-triphosphate-independent pathway at rat dorsolateral septal nucleus.

We have previously reported that a L-2-amino-3-phosphonopropionate (L-AP3)-sensitive metabotropic glutamate receptor was required for the induction of long-term potentiation (LTP) in rat dorsolateral septal nucleus neurons. (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), a selective agonist for metabotropic glutamate receptors, also causes burst firing of dorsolateral septal nucleus (DLSN) neurons. In this study, we investigated whether this response was mediated by a phospholipase C-(PLC) coupled metabotropic glutamate receptor. The threshold concentration of 1S,3R-ACPD for the induction of burst firing was about 5 microM, while 10 microM 1S,3R-ACPD produced a maximal effect. L-AP3 (50 microM) reduced the burst firing induced by 1S,3R-ACPD (5 microM). Although 1S,3R-ACPD stimulated the formation of inositol-1,4,5-triphosphate [Ins(1,4,5)P3] suggesting the presence of PLC-coupled metabotropic glutamate receptors, it was only effective in a higher (30-100 microM) concentration range. In addition, the 1S,3R-ACPD-stimulated formation of Ins(1,4,5)P3 level was not affected by L-AP3. These observations suggest that the 1S,3R-ACPD induced burst firing is not mediated by PLC-coupled metabotropic glutamate receptors.

Action Potentials↗
PubMed1994

The role of P-type calcium channels in the depolarization-induced activation of nitric oxide synthase in frontal cortex.

In this study we demonstrate that 50 mM K+ stimulates the conversion of L-[3H]arginine to L-[3H]citrulline and that this effect is blocked by 10 microM N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, and Ca(2+)-free conditions. Amiloride (1 mM) and low Na+ conditions were used to test the possible involvement of the Na(+)-Ca2+ exchanger. These treatments were without effect. The calcium channel blockers 10 mM Mg2+, 100 microM Cd2+, and 10 mM Co2+ also blocked the K+ response, suggesting the involvement of voltage-dependent calcium channels (VDCCs). The specific VDCC involved seems to be the P type, as funnel-web spider toxin blocked the response whereas 200 microM Ni2+, 10 microM nifedipine, and 100 nM omega-conotoxin did not.

Amiloride↗
PubMed1994

Inhibitory effects of nitric oxide on the uptake of [3H]dopamine and [3H]glutamate by striatal synaptosomes.

Ten-minute incubation with 1 mM S-nitroso-L-cysteine (NO-CYS), a nitric oxide (NO) generator, induced a 3.5-fold increase in the basal dopamine (DA) efflux from rat striatal slices. Reduced hemoglobin (100 microM), a NO scavenger, blocked this response. Nomifensine (10 microM), an inhibitor of high-affinity DA transport, reduced the NO-CYS effect by 39%. In a synaptosomal preparation, NO-CYS induced a concentration-dependent efflux of [3H]DA that was also significantly inhibited by 10 microM nomifensine. Because these findings indicated that NO could alter the activity of the striatal DA transporter, we tested the effect of NO and NO-CYS on the uptake of [3H]DA into crude striatal synaptosomes. Although both compounds inhibited [3H]DA uptake with similar dose-response characteristics (IC50 approximately 300 microM and approximately 400 microM, respectively), the effect of NO was quicker in onset. The presence of superoxide dismutase (30 U/ml) and catalase (50 U/ml) had a small impact on the NO-CYS inhibition of [3H]DA uptake (1.8-fold increase in IC50). NO (1 mM) inhibited striatal [3H]glutamate uptake by 23%, but lower concentrations had no significant effect. The duration of the effect of NO gas on [3H]DA uptake varied from < 5 min to > 10 min, depending on the concentration used. All concentrations of NO-CYS tested produced an inhibition of [3H]DA uptake that lasted at least 10 min. However, only concentrations < or = 1 mM NO-CYS (or NO) were washable. The effect of 3 mM NO-CYS lasted > 20 min and could not be reversed by washing. Reduced hemoglobin (300 microM) prevented the action of 3 mM NO-CYS, whereas methemoglobin had no effect. The action of 3 mM NO-CYS was temperature dependent and took about 2 min to fully develop. Scatchard analysis revealed that NO-CYS diminished the capacity of the DA transporter without having a significant effect on the affinity. NO-CYS had no effect on striatal [3H]-mazindol binding, suggesting that NO-CYS did not interact with the DA recognition site of the transporter. These data suggest that NO may play a role in the regulation of DA and, to a lesser extent, glutamate transport in the striatum.

Animals↗
PubMed1993

A pharmacological analysis of the effects of (+)-AJ 76 and (+)-UH 232 at release regulating pre- and postsynaptic dopamine receptors.

To examine the proposal that (+)-AJ 76 and (+)-UH 232 are dopamine receptor antagonists showing preference for the dopamine autoreceptors over postsynaptic dopamine receptors, the potencies of these two compounds, as well as several typical and atypical antipsychotic drugs, were compared in a model for presynaptic dopamine autoreceptors: reversal of the quinpirole-induced inhibition of [3H]dopamine release from striatal slices, and in two models for postsynaptic dopamine receptors: reversal of the quinpirole-induced inhibition of [14C]acetylcholine release from striatal slices and competition for [3H]spiperone binding in striatal homogenates. The IC50 values of the antipsychotic drugs, as well as (+)-AJ 76 and (+)-UH 232, against [3H]dopamine release correlated closely with their IC50 values against [14C]acetylcholine release and Ki values against [3H]spiperone binding, thus suggesting a close pharmacological similarity between these three populations of dopamine receptors. This implies that previous biochemical and behavioral findings obtained with (+)-AJ 76 and (+)-UH 232 cannot be explained by a selective action of these compounds on terminal dopamine autoreceptors regulating dopamine release, at least relative to the postsynaptic dopamine receptors on cholinergic neurons. Furthermore, comparison of the IC50 values for the drugs tested in our transmitter release assays with previously published values of their affinity for cloned dopamine D2, D3 and D4 receptors suggested that the dopamine receptors controlling both dopamine and acetylcholine release were by far most similar to dopamine D2 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Nitric oxide induces calcium-dependent [3H]dopamine release from striatal slices.

Hydroxylamine (0.01-30 mM), a nitric oxide (NO) generator, produced a concentration-dependent release of [3H]dopamine ([3H]DA) from rat striatal slices. Hemoglobin (10 microM), a NO scavenger, reduced basal [3H]DA release and blocked hydroxylamine (100 microM)-stimulated [3H]DA efflux. Tetrodotoxin (0.5 microM) had no significant effect. Sodium cyanide was used as a model compound to test the possibility that NO acted through blockade of mitochondrial electron transport. Calcium-free experimental buffer (1 mM EGTA) reduced basal release and the hydroxylamine response, while sodium cyanide-induced release did not change under these experimental conditions. Cadmium (200 microM), a non-selective inhibitor of voltage-dependent calcium channels, reduced the hydroxylamine response by 69%. Methylene blue (10 microM), an inhibitor of guanylate cyclase, produced a 3-fold increase in the basal release but had no significant effect on the hydroxylamine response. These data suggest that NO induces calcium-dependent [3H]DA release from the striatum via a mechanism which is independent of blockade of electron transport or activation of guanylate cyclase.

Animals↗
PubMed1993

GBR 12909 fails to antagonize cocaine-induced elevation of dopamine in striatal slices.

The effects of cocaine and 1-(2-bis (4-fluorophenyl)methoxy)-ethyl)-4-(3-phenyl-propyl) piperazine (GBR 12909), alone and together, on [3H] dopamine efflux from superfused rat striatal slices was studied. Both drugs elicited a concentration-dependent increase in spontaneous [3H]dopamine efflux. GBR 12909 when added together with cocaine, had no effect on cocaine-induced [3H] dopamine efflux. It was also determined that GBR 12909 was fully efficacious as an inhibitor of synaptosomal [3H] dopamine uptake and, whether administered in vitro or in vivo, acted in a manner consistent with competitive inhibition. These data are discussed in reference to the recent report that i.p. administration of GBR 12909 antagonized the effect of cocaine on extracellular striatal dopamine levels when infused directly through the dialysis probe, perhaps by acting as a 'partial agonist' at the inhibitory site on the dopamine transporter (Rothman et al., 1991 Pharmacol. Biochem. Behav. 40, 387-397).

Animals↗
PubMed1993

(R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors mediate a calcium-dependent inhibition of the metabotropic glutamate receptor-stimulated formation of inositol 1,4,5-trisphosphate.

L-glutamate (3-1,000 microM) and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 10-1,000 microM), a selective agonist for the metabotropic glutamate receptor, stimulated the formation of inositol 1,4,5-trisphosphate in a concentration-dependent manner. L-Glutamate was half as efficacious as 1S,3R-ACPD. N-methyl-D-aspartate (NMDA; 1 nM to 1 mM) did not significantly influence the response to a maximally effective concentration of 1S,3R-ACPD (100 microM). On the other hand, coapplication of (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA; 1-300 nM) produced a concentration- and time-dependent inhibition of the 1S,3R-ACPD effect, with a maximal inhibition (97%) at 100 nM. Ten micromolar 6-cyano-7-nitroquinoxaline-2,3-dione, an antagonist of the AMPA receptor, blocked the inhibitory effect of AMPA. Reduced extracellular calcium concentration, as well as 10 microM nimodipine, an L-type calcium channel antagonist, inhibited the AMPA influence on the 1S,3R-ACPD response. W-7, a calcium/calmodulin antagonist, prevented the inhibition by AMPA, whereas H-7, an inhibitor of protein kinase C, had no effect. These data suggest that activation of AMPA receptors has an inhibitory influence on inositol 1,4,5-trisphosphate formation mediated by stimulation of the metabotropic glutamate receptor. The mechanism of action involves calcium influx through L-type type calcium channels and possible activation of calcium/calmodulin-dependent enzymes.

Animals↗
PubMed1993

Muscarinic stimulation of gallbladder epithelium. I. Electrophysiology and signaling mechanisms.

To understand the effects of acetylcholine (ACh) on fluid-absorbing epithelia, we carried out experiments on Necturus gallbladder epithelium. Binding studies with 1-quinuclidinyl[phenyl-4(N)-3H]benzilate (QNB) demonstrated that Necturus gallbladder epithelial cells express high-affinity muscarinic receptors. The effects of ACh and carbachol were exerted from the basolateral surface and consisted of a transient hyperpolarization of both cell membranes and a concomitant decrease in the apparent fractional resistance of the apical membrane. Atropine blocked both effects. ACh also elicited transient elevations of inositol 1,4,5-trisphosphate and intracellular free calcium ([Ca2+]i) levels, the latter by both release from intracellular stores and basolateral influx. The phospholipase C antagonist U-73122 inhibited the effects of ACh, whereas inhibition of prostaglandin and guanosine 3',5'-cyclic monophosphate synthesis with indomethacin or methylene blue, respectively, had no effect. In conclusion, Necturus gallbladder epithelium expresses muscarinic receptors in the basolateral membrane. Receptor activation stimulates phospholipase C and elevates cellular levels of inositol 1,4,5-trisphosphate and [Ca2+]i. The elevation in [Ca2+]i activates K+ channels but apparently not Cl- channels.

Acetylcholine↗
PubMed1993

When deaths exceed births: natural decrease in the United States.

"This article delineates the incidence and regional variation [in the United States] of natural decrease since 1950, considers the demographic factors that caused natural decrease, assesses each factor's relative impact, identifies shared characteristics of areas experiencing natural decrease, and considers the implications of natural decrease." Factors considered include shifts in the age structure, fertility declines, increases in mortality, and migration.

Age Distribution↗
PubMed1993

Plasma fibrinogen and other cardiovascular risk factors in urban American Indian smokers.

Although cardiovascular disease is an important health concern for urban American Indians, little information is available on their risk factor levels. We examined several risk factors (plasma fibrinogen, body size and shape, and serum cholesterol) among American Indian smokers in a smoking cessation trial at four urban Indian health clinics. The American Indian smokers had higher levels of fibrinogen and abdominal obesity than African-American and white smokers in two other population-based studies. Serum cholesterol concentrations among the American Indian smokers were lower than typical values among US whites. Among the American Indians, plasma fibrinogen was higher in women (mean: 338 mg/dL) than in men (mean: 318 mg/dL); positively correlated (P < .05) with age, body mass index, and waist-hip ratio; and negatively correlated with serum cholesterol level. Even though average cholesterol levels were not high, the combination of abdominal obesity and high fibrinogen among American Indians, particularly smokers, may increase their risk of cardiovascular disease.

Adolescent↗
PubMed1992

Cocaine and dopamine differentially protect [3H]mazindol binding sites from alkylation by N-ethylmaleimide.

The binding of cocaine, d-amphetamine and dopamine to the site on the dopamine transporter labeled by [3H]mazindol was investigated in rat striatal membranes. N-Ethylmaleimide inhibited about 95% of the specific binding of 5 nM [3H]mazindol in a concentration-dependent manner. The effect of 10 mM N-ethylmaleimide was completely prevented by cocaine (EC50 of 3 microM), but neither 300 microM dopamine nor d-amphetamine afforded any significant protection. On the other hand, high concentrations of cocaine, d-amphetamine and dopamine provided similar protection against inhibition by 0.1 mM N-ethylmaleimide. Taken together these data support the hypothesis that a significant portion of the cocaine binding domain on the transporter is distinct from that of either dopamine or amphetamine. This distinction may be sufficient to allow properly designed drugs to prevent cocaine binding without inhibiting DA transport.

Alkylation↗
PubMed1992

Nitric oxide induces neurotransmitter release from hippocampal slices.

Hydroxylamine (1-300 microM), a nitric oxide generator, stimulated the release of [3H]norepinephrine ([3H]NE) and [14C]acetylcholine ([14C]ACh) from rat hippocampal slices in a concentration-dependent manner (EC50 approximately 30 microM). A maximally effective concentration of hydroxylamine (300 microM) produced a 24-fold increase in the basal [3H]NE and 3.6-fold increase in the in the basal [14C]ACh efflux. Sodium nitroprusside (SNP), also stimulated the release of [3H]NE, but only at high concentrations (10-30 mM). Calcium-free experimental buffer (1 mM EGTA) abolished the response. Hemoglobin (0.3 microM) inhibited the effect of 100 microM hydroxylamine in a manner which was specific for nitric oxide. In addition, 100 microM hydroxylamine increased the efflux of endogenous GABA and glutamate by 3- and 6-fold, respectively.

Acetylcholine↗
PubMed1992

Effect of chronic cocaine treatment on D2 receptors regulating the release of dopamine and acetylcholine in the nucleus accumbens and striatum.

The inhibition of electrically stimulated [3H]DA and [14C]ACh release by a submaximal concentration of quinpirole was measured 1 week after pretreating rats for 9 days with cocaine (15 mg/kg IP, twice per day). Although this pretreatment significantly enhanced behavioral response to a challenge injection of cocaine when compared with rats pretreated with saline only, no significant differences were apparent in the degree of inhibition of electrically evoked [3H]DA or [14C]ACh release by quinpirole in either the nucleus accumbens or striatum. In addition, the potentiation of electrically evoked [3H]DA release and corresponding inhibition of [14C]ACh release by 10 microM cocaine, measured in striatal slices only, was not significantly different between the two treatment groups. These results suggest that the enhanced behavioral response resulting from chronic cocaine treatment (behavioral sensitization) is not caused by a subsensitivity of D2 terminal autoreceptors or by a supersensitivity of postsynaptic D2 receptors on cholinergic neurons.

Acetylcholine↗
PubMed1992

Neurobiology of cocaine abuse.

The recent escalation of cocaine abuse has increased awareness of the need to understand the behavioral effects of cocaine and the determinants of those effects. Cocaine alters both conditioned and unconditioned behavior, and has prominent reinforcing and subjective effects that are particularly relevant to its abuse. An increase in CNS dopamine neurotransmission, resulting from a competitive blockade of high-affinity dopamine uptake mediated by both D1 and D2 dopamine receptors, is a primary determinant of the behavioral effects of cocaine. Either tolerance or sensitization may develop with repeated administration of cocaine. Dependence also develops, although the behavioral changes associated with cocaine withdrawal are subtle. Although numerous CNS changes have been associated with repeated administration of cocaine, the neuropharmacological mechanisms that underlie the behavioral changes that occur with repeated administration remain to be firmly established. Bill Woolverton and Ken Johnson stress that continued collaboration between behavioral pharmacologists and neuroscientists is critical for a complete understanding of the effects of cocaine.

Animals↗