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Biomedical subjects

S Chiu

Publications and source records attributed to S Chiu.

At least 55 records · Page 3Linked to original sources
PubMed1984

In vitro translation of Plasmodium falciparum proteins.

RNA was prepared from cultured Plasmodium falciparum using ribonucleoside-vanadyl ribonuclease inhibitors and assayed in a rabbit reticulocyte, cell-free lysate translation system. Discrete proteins, ranging from less than 10,000 to greater than 200,000 daltons, were synthesized. Some of these proteins were precipitated by immune serum and were similar to those metabolically synthesized. Purified poly [A] mRNA was also translated and differences between the fractions which either bind or pass through a poly [U] Sepharose column are described.

Animals↗
PubMed1984

Characteristics of [3H] propyl beta-carboline-3-carboxylate binding to benzodiazepine receptors in human brain.

Characterization of the binding of derivatives of beta-carboline-3-carboxylate, a putative endogenous ligand for benzodiazepine (BZ) receptors, has not previously been attempted in normal human brain. In the present study, we demonstrated saturable, high affinity binding of [3H] propyl beta-carboline-3-carboxylate [3H] PrCC) in normal human frontal cerebral cortex and cerebellum exhibiting pharmacological specificity similar to [3H] diazepam and [3H] flunitrazepam binding. The binding of [3H] PrCC is increased by chloride and GABA, but decreased by divalent cations, especially calcium. The profile of [3H] PrCC binding in human brain reflects specific interaction with BZ/ionophore/GABA receptor complexes.

Binding, Competitive↗
PubMed1983

Are the pharmacological effects of L-prolyl-L-leucyl-glycinamide (PLG) mediated through specific receptor mechanisms?

In an attempt to delineate the mechanism subserving the demonstrated central effects of the tripeptide, L-prolyl-L-leucyl-glycinamide (PLG) in mammals including humans, we developed a radioligand binding assay to characterize the binding of 3H-PLG to rat brain membranes. Equilibrium binding studies indicated that PLG binds to rat striatum with high affinity (KD = 4.69 +/- 0.50 nM), saturability (Bmax = 9.20 +/- 0.30 fmoles mg-1 protein) and reversibility. Kinetic data yielded a KD = 1.42 +/- 0.21 nM for rat striatum. Regional distribution profile of specific 3H-PLG binding revealed that the striatum has the highest density of PLG binding sites, followed by the hypothalamus and the cerebral cortex. Analogues of PLG compete for specific PLG binding in rat striatum with potencies parallelling their in vivo activities in behavioural systems. Our results support the existence of a unique class of putative peptide receptor sites specific for PLG mediating a spectrum of pharmacological effects.

Animals↗
PubMed1983

Cholinergic control mechanisms for immunoreactive motilin release and motility in the canine duodenum.

The relationship of immunoreactive (IR) motilin release from the duodenum to duodenal motility changes was investigated in anaesthetized dogs. Stimulation of one or both vagi at 5 or 15 Hz or field stimulation of intrinsic duodenal nerves produced significant increases in duodenal vein IR motilin concentrations and accompanying increases in duodenal motility. However, only stimulation of both vagi at 15 Hz produced significant changes in peripheral venous concentrations of IR motilin. These occurred after a delay at a time when both the duodenum and the antrum were quiescent. Either hexamethonium or atropine blocked IR motilin release induced by stimulation of intrinsic or extrinsic nerves while only atropine inhibited the release induced by intraarterial carbachol. The response stimulated by carbachol and blocked by atropine was tetrodotoxin insensitive and the muscarinic receptor involved was presumably located on a nonneural structure. The site sensitive to hexamethonium was presumably the neural pathway which terminated at the muscarinic receptor. Concomitant studies of duodenal motility responses to vagal and field stimulation suggested a conventional neural pathway with preganglionic cholinergic nerves in the vagus, postganglionic cholinergic nerves in the duodenum (activated by field stimulation) and a smooth muscle muscarinic receptor. Activation of antral motility by stimulation of the abdominal vagus or intraarterial carbachol injections to the antrum increased duodenal IR motilin release in the absence of duodenal motility. Thus activation of the intrinsic nerves which cross the pylorus initiated IR motilin release as well as inhibited duodenal motility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

CNS putative L-prolyl-L-leucyl-glycinamide (PLG) receptors, brain and lymphocyte dopamine receptors.

1. In view of previously demonstrated modulatory effects of PLG on the sensitivity of central dopamine receptors, we developed a radioligand binding assay to identify specific binding sites of PLG in rat and normal human brain. 2. 3H-PLG binds specifically to rat striatum exhibiting high affinity (KD = 4.69 +/- 0.50 nM) saturability (Bmax = 9.20 +/- 0.30 fmoles/mg protein) and reversibility; the highest density of specific PLG binding sites occurring in the striatum, followed by the hypothalamus and cerebral cortex. 3. Saturable, high-affinity binding sites of PLG were identified in human striatum. The substantia nigra was enriched with the highest level of specific PLG binding sites. 4. Dopamine receptors were identified in human lymphocytes. 5. The results are compatible with the hypothesis that differential modulation of CNS dopamine receptors by PLG is functionally associated with interacting with specific PLG binding sites in the rat and human brain, and pose implications for Parkinson's disease and tardive dyskinesia.

Animals↗
PubMed1982

Immunoprecipitation of biosynthetically labelled, stage-specific proteins from cultured Plasmodium falciparum using inhibitory human sera.

Proteins from synchronized continuous cultures of Plasmodium falciparum were biosynthetically labelled with [35S]methionine at ring, trophozoite, and schizont stages. Several proteins appeared to be synthesized predominantly at one stage only, especially the schizont stage. Immunoprecipitation using inhibitory human sera revealed that a variety of proteins, from all stages of parasite growth, were recognized. More proteins, especially those with high molecular weight, were precipitated from the schizont stage than from ring and trophozoite stages, but two major proteins (MW or approximately 70,000 daltons and or approximately 45,000 daltons) were recognized in all three stages.

Animals↗
PubMed1982

Cholinergic control of canine antral immunoreactive gastrin release and motility.

We used acute anesthetized dogs to investigate the role of cholinergic receptors in the relationship between antral immunoreactive (I) gastrin release and antral motility. Electrical stimulation of extrinsic nerves via the cervical vagus or the nerve of Latarjet appeared to increase I gastrin release and antral motility by separate pathways as blockade of muscarinic receptors, i.e., atropinization inhibited motility but did not alter I gastrin release. On the other hand, blockade of nicotinic receptors by hexamethonium treatment obliterated I gastrin release induced by stimulation of the extrinsic nerves but only reduced motility. Field stimulation of intrinsic nerves via serosal electrodes also increased both I gastrin release and local motility. Since hexamethonium treatment only slightly reduced both I gastrin release and motility and atropinization eliminated both during field stimulation, the presence of a muscarinic receptor in the final pathway for each is proposed. Atropine eliminated carbachol-induced I gastrin release and motility increases, even in the presence of nerve blockade by tetrodotoxin. This suggests that this muscarinic receptor is on the smooth muscle cell itself and possibly on the gastrin cell. However a proposed role of the somatostatin cell in controlling gastrin release is also consistent with these data. Thus, both an intrinsic cholinergic and a separate extrinsic noncholinergic pathway are involved in antral release of I gastrin but initiation of motility appears to involve a final common pathway terminating in a muscarinic receptor on the smooth muscle cell.

Animals↗
PubMed1981

Neuroleptic drug-induced dopamine receptor supersensitivity: antagonism by L-prolyl-L-leucyl-glycinamide.

An animal model of tardive dyskinesia was used to evaluate the potential antidyskinetic properties of the neuropeptide L-prolyl-L-leucyl-glycinamide (PLG). In rats, PLG administered concurrently with the neuroleptic drug haloperidol or chlorpromazine antagonized the enhancement of specific [3H]spiroperidol binding in the striatum that is associated with long-term neuroleptic treatment. The results are discussed in relation to a possible functional coupling of the putative PLG receptor with neuroleptic-dopamine receptor complex and clinical implications for tardive dyskinesia.

Animals↗
PubMed1981

Effect of L-prolyl-L-leucyl-glycinamide (PLG) on neuroleptic-induced catalepsy and dopamine/neuroleptic receptor bindings.

The mechanism of action subserving the potential anti-Parkinsonian properties of L-prolyl-L-leucyl-glycinamide (PLG) was investigated in behavioural and neurochemical models of dopaminergic function in the rat. Acute administration of PLG (20 and 40 mg kg-1 SC) failed to alter appreciably the intensity of the cataleptic response elicited by haloperidol (3 mg kg-1 IP). By contrast, chronic PLG treatment (20, 40 and 80 mg kg-1 SC twice daily for five days) significantly attenuated haloperidol-induced catalepsy. The effect of PLG on in vitro dopamine/neuroleptic receptor binding in rat striatum as differentially labelled by apomorphine and spiroperidol was also examined. PLG selectively enhanced the affinity of the specific binding of agonist [3H] apomorphine to dopamine receptors in the striatum, but had no effect on [3H] spiroperidol binding. The behavioural and biochemical results obtained in the present study raise the possibility that PLG may facilitate nigro-striatal dopaminergic neurotransmission through interacting with a unique PLG receptor functionally coupled to the dopamine receptor-adenylate cyclase complex.

Animals↗
PubMed1980

Effects of dopaminergic and cholinergic drugs. naloxone and l-prolyl-leucyl-glycinamide on LSD-induced catalepsy.

In an attempt to elucidate the mechanism of d-lysergic acid diethylamide (LSD) induced catalepsy, the effects of cholinergic and dopaminergic agents, naloxone and L-propyl-leucyl-glycinamide (PLG) were studied in rats. The dose-dependent (50--500 micrograms kg-1 s.c.) and time-related cataleptic response elicited by LSD was preceded by a phase of hyperexcitability. The non-hallucinogenic analogue, 2-bromo-LSD (BOL), was without effect. Both apomorphine, the dopamine agonist, and L-DOPA antagonized LSD-induced catalepsy whereas the dopamine depleting agent alpha-methyl-p-tyrosine (alpha-MPT) slightly prolonged the cataleptic effect. Cholinergic muscarinic receptor stimulation with pilocarpine antagonized LSD-induced catalepsy. The muscarinic antagonists, atropine and scopolamine, intensified the hyperexcitable phase and potentiated the cataleptic effects of LSD. Nicotine slightly potentiated LSD action but mecamylamine antagonized it. While pre-treatment with naloxone, the narcotic antagonist and PLG prolonged the cataleptic response, post-treatment with naloxone effectively attenuated LSD-induced catalepsy. The behavioural data are interpreted to suggest that LSD-induced catalepsy may be mediated through diminished dopaminergic and cholinergic neuronal activity and under enkephalinergic modulation. The neuroanatomical foci and exact mechanism of action remain to be delineated.

Animals↗
PubMed1979

Antagonism of morphine-induced catalepsy by L-prolyl-L-leucyl-glycinamide.

In view of the recently demonstrated extra-endocrine central actions of hypothalamic releasing hormones, we have investigated the effects of prolyl-leucyl-glycinamide (PLG) and thyrotropin releasing hormone (TRH) on morphine-induced catalepsy. Although acute administration of PLG (10 mg kg-1 s.c.) slightly attenuated the cataleptic response, chronic PLG treatment (10 mg kg-1 s.c. for 10 days) virtually abolished morphine-induced catalepsy. TRH, administered subcutaneously, exhibited little or no anti-cataleptic activity. These results are discussed in relation to the possible central site of narcotic-induced catalepsy and the therapeutic potential of PLG in Parkinson's disease.

Animals↗
PubMed1978

Experimental acetaminophen-induced hepatic necrosis: biochemical and electron microscopic study of cysteamine protection.

In an attempt to elucidate the biochemical mechanism of acetaminophen-induced hepatic necrosis, the present study in hamsters was undertaken to evaluate the possible changes in lipid peroxidation and microsomal enzyme activities. The protective action of cysteamine was likewise assessed in the light of these biochemical variables and the fine structural features of the liver were seen by electron microscopy. One group of golden Syrian hamsters was administered a toxic dosage of acetaminophen (600 mg . per kg . intraperitoneally) while another group was treated with the same dosage of acetaminophen, followed 1 hour later by cysteamine (200 mg . per kg . intraperitoneally). The animals were sacrificed at 6, 12, 18, and 24 hours. Microsomal fractions were isolated for biochemical assays, and liver sections were prepared for electron microscopy. Results showed that significant enhancement of lipid peroxidation occurred in the untreated acetaminophen-poisoned group, as compared to the cysteamine-treated group. Glucose 6-phosphatase activity was markedly suppressed at 6, 12, and 18 hours after acetaminophen administration. Cysteamine treatment completely prevented the curtailment of NADPH-cytochrome c reductase and glucose 6-phosphatase activities in the protected group, and partially maintained aniline hydroxylase activity. Cytochrome P-450 level was unaffected in both the cysteamine-treated and the untreated groups at the respective time intervals. Electron microscopic examination showed progressive loss of the structural integrity of the endoplasmic reticulum, lipid infiltration, and vacuolation in the untreated acetaminophen-poisoned group. At 18 and 24 hours, sinusoidal congestion and myeloid figure formation were prominent. In the cysteamine-protected group, polysomes reassembled around the granular endoplasmic reticulum at 18 hours. It is postulated that lipid peroxide formed in vivo may facilitate the microsomal oxidation of acetaminophen to the toxic metabolite. NADPH-cytochrome c reductase is likely to be the locus within the NADPH-cytochrome P-450 electron transport chain susceptible to lipoperoxidation. The free radical-related lipoperoxidation may mediate the impairment of in vitro drug metabolism, as reflected by the depressed aniline hydroxylase activity. The abnormal phospholipid metabolism is manifested at the fine structural level by the myeloid body formation. The protective effects of cysteamine as seen in the attenuated lipid peroxidation and the consequent derangement of microsomal enzymes correlate well with the morphologic observations. Cysteamine protection is discussed in terms of its role as an inhibitor of the toxic metabolite formation.

Acetaminophen↗