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L R Chang

Publications and source records attributed to L R Chang.

9 recordsLinked to original sources
PubMed1991

Chronic effect of [D-Pen2,D-Pen5]enkephalin on rat brain opioid receptors.

In previous studies, we have demonstrated that chronic etorphine or [D-Ala2,D-Leu5]enkephalin (DADLE) treatment of rats results in the reduction of mu- and delta-opioid receptor binding activities as tolerance develops. As both etorphine and DADLE are relatively non-specific opioid ligands, interacting with both mu- and delta-receptors, these studies could not determine whether down-regulation of a specific receptor type occurs. Therefore, in the present studies, animals were rendered tolerant to the delta-opioid receptor-selective agonist [D-Pen2,D-Pen5]enkephalin (DPDPE), and receptor binding activities were measured. Treating Sprague-Dawley rats with increasing doses of DPDPE (80-160-240-320 micrograms/kg) i.c.v. for 1 to 4 days resulted in a time-dependent increase in the AD50 of DPDPE to elicit an antinociceptive response. When delta-receptor binding was determined by using [3H]DPDPE, a 40-50% decrease in binding in the midbrain and cortex, and 25-35% decrease in binding in the striatum were observed after 3 or 4 days of DPDPE treatment. Scatchard analysis of the [3H]DPDPE saturation binding data revealed a decrease in Bmax values and no significant change in Kd values. To our surprise, when mu-receptor binding was determined by using [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO), a 10-15% decrease in binding was also observed in the midbrain and cortex after 4 days of DPDPE treatment. Our conclusion is that chronic DPDPE treatment preferentially reduces delta-opioid receptor binding activity. Its minor effect on the mu-opioid receptor maybe due to an interaction between delta cx and mu cx binding sites.

Analgesics↗
PubMed1990

Decrease in mu-opioid receptor binding capacity in rat brain after chronic PL017 treatment.

In previous studies, we have demonstrated that chronic treatment of rats with either etorphine or D-Ala2, D-Leu5-enkephalin (DADLE) resulted in the reduction of opioid receptor binding activities during the course of tolerance development. In both cases, mu-opioid receptor binding capacity was attenuated together with the delta-opioid receptor binding capacity. Because both etorphine and DADLE are relatively non-specific opioid ligands, interacting with both mu and delta receptors, these studies could not determine whether down-regulation of a specific receptor type is possible. Therefore, in the current studies, animals were rendered tolerant to the mu-opioid receptor-selective ligand PL017 and the receptor binding capacity was measured afterwards. Treating Sprague-Dawley rats with increasing doses of PL017 (2.5-20 micrograms/kg) i.c.v. for 5 days resulted in a 30- to 40-fold increase in the AD50 of the peptide to elicit the antinociceptive response and about 14-fold increase in the ED50 of the peptide to elicit the catatonic effect. When mu- and delta-binding was determined using [3H]diprenorphine in the presence of morphiceptin or DPDPE respectively, a significant decrease (20-30%) in the mu-opioid receptor binding but not in delta-opioid receptor binding was observed in all the brain areas tested after 5 days of PL017 treatment. Scatchard analysis of the [3H]DAMGO saturation binding data revealed a decrease in Bmax values and no change in the Kd values. Hence, mu-opioid receptors can be specifically regulated by ligand in the brain as delta-receptors are in neuroblastoma x glioma NG 108-15 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Decrease in delta-opioid receptor density in rat brain after chronic [D-Ala2,D-Leu5]enkephalin treatment.

Chronic treatment of Sprague-Dawley rats with [D-Ala2,D-Leu5]enkephalin (DADLE) resulted in the development of tolerance to the antinociceptive effect of this opioid peptide. When opioid receptor binding was measured, time-dependent decreases in [3H]diprenorphine binding to the P2 membranes prepared from the cortex, midbrain and striatum were observed. Scatchard analysis of the saturation binding data revealed a decrease in Bmax values and no change in the Kd values of [3H]diprenorphine binding to these brain regions, indicative of down-regulation of the receptor. This reduction in the opioid receptor binding activities could be demonstrated to be due to the DADLE effect on the delta-opioid receptors in these brain regions. When [3H]DADLE binding was carried out in the presence of morphiceptin, a significant reduction in the delta-opioid receptor binding was observed in all brain areas tested. mu-Opioid receptor binding decrease was observed only in the striatum after 5 days of DADLE treatment. Additionally, the onset of delta-opioid receptor decrease in the midbrain area was rapid, within 6 h of the initiation of the chronic DADLE treatment. Thus, analogous to previous observations in which chronic etorphine treatment preferentially reduced mu-opioid receptor binding, chronic DADLE treatment preferentially reduced delta-opioid receptor binding activity.

Animals↗
PubMed1986

Heterogeneity of [3H]ethyl beta-carboline-3-carboxylate binding sites and [3H]gamma-aminobutyric acid binding sites.

Binding properties of [3H]flunitrazepam ([3H]FNZ), [3H]ethyl beta-carboline-3-carboxylate ([3H]beta CCE), [3H]muscimol ([3H]MUSC) and [3H]gamma-aminobutyric acid ([3H]GABA) to bovine cortical membranes and to their Triton extracts were studied. GABA, 1 X 10(-5) M, stimulated [3H]FNZ binding of frozen, thawed and washed membranes by an increase in affinity without alteration of the maximal number of binding sites, and this GABA stimulated [3H]FNZ binding can be inhibited by bicuculline methobromide. Freeze, thaw and wash with Triton X-100 removed the low affinity [3H]MUSC binding sites. The ratios of [3H]FNZ binding sites to [3H]beta CCE binding sites and [3H]MUSC binding sites to [3H]GABA binding sites were always found to be about 1:2 in both membranes and soluble extracts. The fact that [3H]beta CCE, after displaced by clonazepam, can be further displaced by unlabelled beta CCE from its binding sites and that a portion of [3H]beta CCE binding sites can be survived from FNZ-photolysis implied that there are at least two subclasses of beta CCE binding sites, one is sensitive to beta CCE only and the other is sensitive to both beta CCE and benzodiazepines (BZs). [3H]GABA, after displaced by MUSC, can be further displaced by unlabelled GABA from its binding sites. The results also support that there are two subclasses of BZ-related GABA binding sites, one is sensitive to GABA only and the other is sensitive to both GABA and MUSC. Furthermore, the decay rates of [3H]beta CCE and [3H]GABA binding activities exposed to various degree of electron bombardment are identical, which is evident that these two binding sites are believed to be functional associated in a macromolecular complex with molecular mass about 220,000 Mr.

Animals↗
PubMed1986

Determination of the sizes of the opioid receptors in their membrane environment by radiation inactivation.

Opioids, like other drugs, are thought to initiate their effects by association with their specific receptors. However, very little is known about the opioid receptor as a molecular entity. The binding components have been solubilized in detergent and purified by different approaches, but the molecular size of soluble opioid receptor complexes reported by different groups varied from 23,000 to 750,000. In this study, the technique of radiation inactivation by gamma rays was used to investigate the apparent size of the opioid receptor in rat brain membranes under different conditions. The molecular sizes of opioid receptor complexes were estimated as 313,000 +/- 13,500 in the presence of [D-Ala2, D-Leu5] enkephalin, NaCl and Gpp (NH)p; as 165,000 +/- 8,500 in the presence of NaCl only, or of both NaCl and Gpp (NH)p; as 217,000 +/- 6,600 in the presence of Gpp (NH)p only; and as 286,000 +/- 60,900 in the presence of MgCl2 only. A simple model has been proposed to explain these different apparent target sizes of opioid receptors obtained under different conditions.

Animals↗
PubMed1977

Effect of GABA on the electrical potentials across the mouse small intestine.

The effects of gamma-aminobutyric acid (GABA) on transmural potential difference (PD) and radioactive chloride fluxes (J) across the mouse small intestine were studied. It was found that GABA decreased the PD and increased the J in both mucosal-to-serosal and serosal-to-mucosal directions (JMS and JSM) only at a concentration of or higher than 50 mM. The PD was increased by the presence of 10 mM glucose or glycine in bathing solutions. The PD was also decreased by increasing the osmolarity of the bathing solutions with increasing concentration of GABA, mannitol, sucrose, or glucose. Our results suggested that the hyperosmotic effect causes the decrease of PD and the increase of J across the mouse small intestine by GABA.

Aminobutyrates↗
PubMed1975

The effect of diuretics on sodium transport across the mouse intestine.

The effects of three natriuretic agents on Na transport across the mouse intestine were determined. It was found that ethacrynic acid at a concentration of 1mM, markedly reduced the net transmural transport of Na ion by decreasing themucosa-to-serosa flux with little or no effect on serosa-to-mucosa flux. Furosemide or amiloride at a concentration of 1 mM produced similar but less profound effects. A reduction of net Na22 flux was observed in the presence of either diuretic, but with furosemide and amiloride this inhibitory effect observed only if glucose was present in the bathing solution. It is, therefore, concluded that the intestinal transport of Na ion involves two processes, one is glucose or substrate-dependent, and the other glucose or substrate-independent. Ethacrynic acid inhibits the substrate-independent process while furosemide and amiloride affect only the substrate-dependent process of Na transport.

Amiloride↗