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Biomedical subjects

J S Han

Publications and source records attributed to J S Han.

At least 199 records · Page 11Linked to original sources
PubMed1993

Increased release of immunoreactive cholecystokinin octapeptide by morphine and potentiation of mu-opioid analgesia by CCKB receptor antagonist L-365,260 in rat spinal cord.

This is the first report showing, in an in vivo study, that systemic morphine produced a marked (89%, P < 0.01) increase of the cholecystokinin octapeptide (CCK-8) immunoreactivity in the perfusate of the rat spinal cord, an effect completely reversed by naloxone. Since CCK-8 has been shown to possess potent anti-opioid activity at a spinal level, a blockade of the spinal cholecystokinin effect would be expected to potentiate opiate analgesia. With tail flick latency as a nociceptive index, it was found that intrathecal (i.t.) injection of a novel CCKB antagonist L-365,260 produced a marked potentiation of the analgesic effect induced by the mu-opioid agonists morphine (4 mg/kg s.c.) or ohmefentanyl (32 ng i.t.). Similar effects were obtained with the CCKA antagonist devazepide at a dose 40-50 times higher than that of L-365,260. Both devazepide and L-365,260 showed a bell-shaped dose-response curve. The results confirm the notion that an increased release of CCK-8 may constitute a self-limiting process for opioid effects at the spinal level, and that it is the CCKB receptor which mediates the anti-opioid effect of CCK-8 in the rat spinal cord.

Analgesia↗
PubMed1993

Suppression by [D-Pen2, D-Pen5]enkephalin on cyclic AMP dependent protein kinase-induced, but not protein kinase C-induced increment of intracellular free calcium in NG108-15 cells.

In neuroblastoma X glioma NG108-15 cell lines, KCl 50 mM produced a significant increase in [Ca2+]i which was blocked completely by voltage-dependent Ca2+ channel antagonist verapamil. High K(+)-induced increase in [Ca2+]i can be suppressed by selective delta opioid agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) (an effect completely reversed by opioid antagonist naloxone), but not by the mu agonist ohmefentanyl (OMF) or kappa agonist 66A-078. Aside from high K+ stimulation, a number of chemicals can produce an increase in [Ca2+]i, i.e., selective adenylate cyclase activator forskolin, the membrane permeable cyclic AMP (cAMP) analogue dibutyryl-cAMP (Bt2cAMP) and the activator of protein kinase C (PKC) 12-O-tetradecanoylphorbol 13-acetate (TPA). All these effects can be readily blocked by verapamil. DPDPE blocks the increase in [Ca2+]i induced by forskolin and Bt2cAMP, but not that by TPA. The results suggest that cAMP dependent protein kinase-, but not PKC-induced Ca2+ influx mechanism seems to be involved in the delta receptor mediated opioid effect.

Analgesics↗
PubMed1993

Cyclic AMP mediates mu and delta, but not kappa opioid analgesia in the spinal cord of the rat.

Intrathecal (i.t.) injection of the membrane-permeable cyclic AMP (cAMP) analogue dibutyryl-cyclic AMP (Bt2cAMP) in 3 successive doses of 12.5, 12.5 and 25 ug in rats was very effective in reversing the antinociceptive effects produced by mu agonist morphine or delta agonist DPDPE, but not that by kappa agonist dynorphin A-(1-13). cAMP content of the spinal cord was significantly decreased by morphine, but not by dynorphin A-(1-13). The results imply that a decrease in spinal cAMP content may be important for the antinociceptive effect elicited by mu and delta, but not kappa opioid receptor agonists.

Analgesia↗
PubMed1993

Effect of CCK-8 on audiogenic epileptic seizure in P77PMC rats.

P77PMC rat is a breed of rat with congenital audiogenic seizure(AS). AS attacks were suppressed by cholecystokinin octapeptide (CCK-8) injected intraperitoneally (i.p.) at a dose of 50 micrograms/kg, but not at 25 micrograms/kg. Radioimmunoassay study showed that the CCK-8 immunoreactivity (IR) in the cerebrocortex and hippocampus is much lower in P77PMC rats than that of Wistar rats. The results suggest that a low cerebral content of CCK-8 may account for the high susceptibility of audiogenic seizure in P77PMC rats.

Acoustic Stimulation↗
PubMed1993

Increased release of immunoreactive CCK-8 by electroacupuncture and enhancement of electroacupuncture analgesia by CCK-B antagonist in rat spinal cord.

Cholecystokinin octapeptide (CCK-8) in CNS has been shown to function as a neuropeptide with potent anti-opioid activity. It hinders opioid analgesia and facilitates opioid tolerance. The present study showed that electroacupuncture (EA) stimulation produced a marked increase of the CCK-8 immunoreactivity (ir) in the perfusate of the rat spinal cord. The increase of CCK-8-ir was most marked in response to EA of 100 Hz and 15 Hz, and less marked in response to EA of 2 Hz. Since CCK-8 has been shown to possess potent anti-opioid activity at the spinal level, blockade of the spinal CCK effect would be expected to potentiate EA-induced analgesia which is known to be opioid-mediated. Intrathecal (i.t.) administration of CCK-B antagonist L-365,260 per se did not affect tail flick latency (TFL) to any significant extent, yet it potentiated EA induced analgesia in a dose- and frequency-dependent manner. The potentiation was most marked at a dose range of 2.5-5.0 ng (i.t.) and at a frequency rank order of 100 Hz > 15 Hz > 2 Hz. The results suggest that an increased release of CCK-8 following EA may limit the effect of opioid peptides, and that the CCK-B receptor mediates the anti-opioid effect of CCK-8 in rat spinal cord.

Acupuncture Analgesia↗
PubMed1993

Suppression of morphine abstinence syndrome by body electroacupuncture of different frequencies in rats.

The effectiveness of electroacupuncture (EA) stimulation in suppressing the morphine abstinence syndrome was studied. Male Wistar rats were made dependent on morphine either by multiple injections or pellet implantation. EA of 2 Hz or 100 Hz was administered for 30 min followed by naloxone challenge (0.5 mg/kg, i.p.) and the withdrawal syndrome was scored for a period of 45 min. In rats receiving multiple injection regime, 100-Hz EA produced a statistically significant suppression of wet shakes (-61%), teeth chattering (-59%), escape attempts (-48%), weight loss (-3.3%) and penile licking (-28%) (P < 0.05). EA of 2 Hz produced only a mild but significant suppression in escape attempts (-42%) and wet shakes (-31%). Similar results were obtained in rats receiving pellet implantation. Since 100-Hz EA has been shown to accelerate the release of dynorphins in the CNS, the results seem to be compatible with the notion that dynorphin may play an important role in suppressing the opioid withdrawal syndrome.

Animals↗
PubMed1993

Decreased acetylation of isoniazid in chronic renal failure.

Pharmacokinetic parameters of isoniazid obtained from 37 normal subjects were compared with parameters obtained from 14 patients with chronic renal failure. In the 29 normal rapid acetylators and eight normal slow acetylators, the mean plasma half-life values of isoniazid were 1.54 +/- 0.31 and 3.68 +/- 0.59 hours, respectively. The plasma half-life values of isoniazid in patients with chronic renal failure varied widely from 1.30 to 10.13 hours, but the values were significantly longer than those of normal subjects. Because isoniazid clearance is governed mainly by hepatic metabolism, such a significant prolongation of plasma half-life of isoniazid was unexpected; thus the pharmacokinetics of isoniazid were reevaluated in the same patients with chronic renal failure after the kidney transplantation. After successful kidney transplantation, the shortening of isoniazid half-life was pronounced and the nonrenal clearance was markedly increased. These findings indicate that decreased isoniazid clearance in chronic renal failure is caused in minor part by the decreased renal excretion of isoniazid and in major part by the depressed hepatic N-acetylation of isoniazid.

Acetylation↗
PubMed1993

Localization of Hantaan viral envelope glycoproteins by monoclonal antibodies in renal tissues from patients with Korean hemorrhagic fever H.

The role of viruses in several renal diseases is not documented clearly. The authors attempted to localize envelope glycoproteins of Hantaan virus in biopsy specimens from patients with Korean hemorrhagic fever (KHF) as evidence of direct viral invasion of renal tissues. The authors studied sequential sections of kidney biopsy specimens from 23 of 35 patients with serologically confirmed KHF diagnosed between June 1985 and December 1989. The sections were stained with the avidin-biotin-peroxidase complex method with monoclonal antibodies to G1 and G2 envelope glycoproteins. Control antibodies of the same isotype were used to rule out nonspecific staining, and hyperimmune rabbit sera or convalescent sera of patients with KHF were used for blocking tests. Normal renal tissues and kidney biopsy tissues from minimal-change nephrotic syndrome were used as negative control sections. The kidney biopsies were performed between the fifth and thirtieth days after onset of fever. The authors detected viral glycoproteins in renal tissues from 22 of the 23 patients. The viral glycoproteins were localized in the cytoplasm of the tubular epithelial cells, and the distribution of viral glycoproteins in the tubules was focal. Glycoproteins also were localized in the cytoplasm of the sloughed renal tubular epithelial cells, where tubular degenerative changes were prominent. These findings suggest the direct invasion of renal tubules by the virus and may partly explain the pathogenesis of acute renal failure in KHF.

Adolescent↗
PubMed1993

Vasopressin and oxytocin receptors coupled to Ca2+ mobilization in rat inner medullary collecting duct.

In renal collecting duct epithelial cells, arginine vasopressin (AVP) at greater than nanomolar concentrations has been reported to transiently increase intracellular free calcium ([Ca2+]i) in a manner consistent with activation of the phosphoinositide pathway. To investigate whether any of the known neurohypophysial hormone subtypes are involved, we measured [Ca2+]i in microdissected rat terminal inner medullary collecting duct (IMCD) using fura-2. To allow quantitative comparisons of the response under different conditions, we determined the areas under the response curves (in nM.min) over 1.5 min using numerical integration. AVP, the V1b-receptor agonist [deamino1,D-3-(pyridyl)Ala2,Arg8]vasopressin, the V2-receptor agonist 1-desamino-8-D-arginine vasopressin, oxytocin, and the selective oxytocin-receptor agonist [Thr4,Gly7]oxytocin (TG-OXT), each at 10 nM, significantly increased [Ca2+]i (69.52 +/- 10.25, 27.0 +/- 11.7, 24.33 +/- 5.83, 14.75 +/- 2.81, and 14.57 +/- 3.50 nM.min, respectively). In contrast, a V1a-selective agonist ([Phe2,Ile3,Orn8]vasopressin) did not increase [Ca2+]i (0.43 +/- 2.36 nM.min). In desensitization studies, challenge with 10 nM AVP or TG-OXT completely prevented a rise in [Ca2+]i in response to immediate rechallenge with the same agent, but not the other, demonstrating homologous desensitization. The lack of cross-desensitization implies that at least two receptors are present that can trigger a rise in [Ca2+]i in response to neurohypophysial hormones. Antagonists for oxytocin ([des-glycinamide9,d(CH2)5(1),O-Me-Tyr2,Thr4,Orn8]vaso tocin), V2 ([d(CH2)5(1),D-Ile2,Ile4,Arg8]vasopressin), and V1a ([d(CH2)5(1),O-Me-Tyr2,Arg8]vasopressin) receptors partially inhibited the [Ca2+]i response induced by 10 nM AVP (89.5, 81.6, and 51.4% inhibition, respectively). These data are consistent with the view that both an oxytocin receptor and a vasopressin receptor are coupled to a [Ca2+]i mobilization response in rat terminal IMCD. This vasopressin receptor is distinct from both the V1a receptor and the V2 receptor and may be either the V1b receptor or a novel vasopressin receptor subtype.

Animals↗
PubMed1993

Dual actions of vasopressin and oxytocin in regulation of water permeability in terminal collecting duct.

We conducted studies in isolated perfused terminal inner medullary collecting ducts (IMCD) from rats to investigate the roles of oxytocin and vasopressin in the regulation of osmotic water permeability. Vasopressin and oxytocin were found to have both stimulatory effects (at 0.1 nM) and inhibitory effects (at 10 nM) on osmotic water permeability. Measurements of adenosine 3',5'-cyclic monophosphate (cAMP) production demonstrated that both vasopressin and oxytocin increase cAMP production. Both the selective oxytocin-receptor agonist [Thr4,Gly7]oxytocin (10 nM) and the selective V1b agonist [deamino1,D-3-(pyridyl)Ala2,Arg8]vasopressin (10 nM) inhibited vasopressin-stimulated osmotic water permeability. In contrast, the selective V1a vasopressin-receptor agonist [Phe2,Ile3,Orn8]vasopressin (10 nM) had no effect on vasopressin-stimulated osmotic water permeability. These effects on water permeability correlated with the ability of the agents to transiently increase intracellular free calcium. The oxytocin/vasopressin-receptor antagonist [des-glycinamide9,d(CH2)5(1),O-Me-Tyr2,Thr4,Orn8]vasot ocin, which almost completely blocks vasopressin-induced calcium mobilization, also blocked the ability of 10 nM vasopressin to inhibit osmotic water permeability relative to that found with 0.1 nM vasopressin. We conclude the following. 1) Oxytocin, like vasopressin, has dual effects on osmotic water permeability, increasing it at subnanomolar concentrations and inhibiting it at suprananomolar concentrations. 2) Oxytocin, like vasopressin, can increase cAMP production, perhaps accounting for the increase in water permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Reversal of electroacupuncture tolerance by CCK-8 antiserum: an electrophysiological study on pain-related neurons in nucleus parafascicularis of the rat.

Two varieties of neurons were found in nucleus parafascicularis (pf) of the rat: one responds to noxious stimuli with an increase in firing (pain-excited neuron, PEN), the other with a decrease in firing (pain-inhibited neuron, PIN). Electroacupuncture (EA) has been shown to suppress PEN and excite PIN, which can be taken as an electrophysiological index for EA analgesia. This effect of EA subsided after prolonged (6 h) EA stimulation, suggesting the development of tolerance to EA. Intracerebroventricular (icv) injection of CCK-8 antiserum aiming at neutralizing endogenously released CCK-8 resulted in a complete restoration of the EA effect. Normal rabbit serum was not effective. CCK-8 antiserum per se did not affect the firing pattern of the PEN or PIN in nontolerant rat. The results obtained from single neuron recording in anesthetized animals thus confirmed those obtained in intact animals using the tail flick as the end point, implying that an excess of endogenously released CCK-8 may constitute one of the mechanisms for the development of EA tolerance.

Animals↗
PubMed1993

Electroacupuncture accelerated the expression of c-Fos protooncogene in dopaminergic neurons in the ventral tegmental area of the rat.

The mesolimbic dopaminergic system has been implicated in mediating morphine and electroacupuncture analgesia. In the present study, Fos immunoreactivity was used as a marker of neuronal activity to investigate if electroacupuncture could activate the dopaminergic neurons in the midbrain. Electroacupuncture stimulation significantly increased the number of Fos-positive dopaminergic neurons in the ventral tegmental area (VTA), whereas no significant c-fos expression in the dopaminergic neurons was observed in the substantia nigra (SN). These results indicate that the VTA rather than the SN may play a role in mediating electroacupuncture analgesia.

Acupuncture Analgesia↗
PubMed1993

Induction of c-fos expression in the rostral medulla of rats following electroacupuncture stimulation.

The present study was designed to examine the induction of c-fos mRNA and Fos-like protein in the rostral medulla of awake rats following electroacupuncture (EA) stimulation, using in situ hybridization and immunohistochemical method. Rats were subjected to EA stimulation (100 Hz, 1-2-3 mA) for 30 min by inserting two needles into acupoints Zusanli (S36) and Sanyingjiao (Sp6) of each hind leg. Animals were sacrificed 1h and 2h after EA for in situ hybridization and immunohistochemical study, respectively. c-fos mRNA or Fos-like-immunoreactivity (FLI) neurons were densely distributed in the rostral ventromedial medulla (RVM), including raphe magnus nucleus, gigantocellular reticular nucleus, gigantocellular reticular nucleus alpha, as well as intermediate reticular nucleus. Neurons in the solitary tract nucleus also showed c-fos expression. The results suggest that the RVM may be an important region for mediating EA effect.

Afferent Pathways↗
PubMed1993

[Cholecystokinin octapeptide (CCK-8) antagonizes morphine analgesia in amygdala of the rat].

CCK-8 administered bilaterally to the amygdala at 0.1-1.0 ng dose-dependently antagonized the analgesia induced by morphine (4 mg/kg, s. c.) as measured by the changes in tail flick latency (TFL). This effect of CCK-8 could be reversed by Devazepide, a CCK-A receptor antagonist dose-dependently at 50 ng and 200 ng, and by L-365, 260, a CCK-B receptor antagonist at 5 ng and 8 ng administered to the same site. The effect of morphine analgesia was potentiated by 200 ng Devazepide or 8 ng L-365, 260 administered bilaterally to amygdala. Devazepide and L-365, 260 per second showed no significant influence on basal TFL. The results indicate that amygdala is a strategic site where CCK-8 exerts an antiopioid activity. Since the effect of L-365, 260 was 25 times more potent than Devazepide, it suggests that the anti-opiod effect of CCK in amygdala is mediated by CCK-B receptors.

Amygdala↗
PubMed1993

The antagonistic effect of cholecystokinin octapeptide (CCK-8) on opioid effects in cardiovascular activities was mediated by CCK-B receptor.

Previous studies have shown that CCK-8 has distinct antiopioid effect in the central sites related with pain control and blood pressure control. The aim of this study was to explore the receptor mechanism by which CCK-8 antagonized the depressor effect of u- and k-opioid agonists, and to observe whether CCK-8 could antagonize the depressor effect induced by muscimol, a nonopioid substance. The results showed that (i) The antagonistic effect of CCK-8 on opioid-induced hypotension could be blocked by intrathecal (i. t.) administration of CCK-B antagonist L-365, 260 at nanogram doses, or by CCK-A antagonist devazepide at doses 20-40 times higher than L-365, 260, indicating that it was the CCK-B receptor which mediates the antiopioid effect. (ii) The depressor effect induced by intrathecal muscimol, a GABA agonist, was blocked neither by naloxone nor by CCK-8, supporting the notion that CCK-8 is an endogenous opioid antagonist rather than a universal anti-hypotension agent.

Animals↗
PubMed1993

[Potentiation of morphine- and ohmefentanyl-induced analgesia by cholecystokinin receptor antagonists in rat].

It has been reported that intrathecal (i.t.) injection of CCK-8 showed a marked antagonism to analgesic effects mediated by mu-opioid receptors in rat. The present study was performed to ascertain whether the blockade of endogenously released CCK-8 by potent and selective CCK-A antagonist devazepide and CCK-B antagonist L-365260 would affect opioid analgesia at the spinal cord level. A marked potentiation of the analgesic effect induced by morphine (4 mg/kg, sc) was produced by i.t. injection of 100 ng devazepide or 2.5 ng L-365260. Dose-response curves for the enhancement of the two drugs on morphine analgesia were bell-shaped. Intrathecal injection of 66 ng devazepide or 1.25 ng L-365260 was also shown to potentiate the analgesic effect induced by the selective mu-opioid agonist ohmefentanyl (OMF) (32 ng, i.t.). The dose-response curves were also bell-shaped. Devazepide or L-365260 per se produced no significant changes in rat tail flick latency (TFL). The above results are interpreted to mean that endogenously released CCK-8 in the spinal cord plays an antagonistic role to opioid analgesia, and it is the CCK-B receptors that mediate the anti-opioid effect since the dose of devazepide is 40-50 times higher than that of L-365260.

Analgesics↗
PubMed1993

[Electroacupuncture enhances enkephalin mRNA expression in the spinal cord and medulla, an in situ hybridization study].

Previous studies in this laboratory have shown that electroacupuncture (EA) accelerated the release of enkephalin in the spinal cord. The present study was undertaken to investigate the effect of EA stimulation on the expression of preproenkephalin (PPE) mRNA in the rat spinal cord and medulla by in situ hybridization histochemical technique. Animals were administrated with 2 Hz EA stimulation (1-2-3 mA, 30 min) applied at acupoints sanyingjiao and zusanli of one hind leg. The rats were perfused 24 h after EA, and quantitative changes of PPE-mRNA expression were determined by emulsion autoradiography. EA stimulation was found to increase the number of neurons expressing PPE-mRNA in spinal cord and medulla. Increased expression of PPE-mRNA was more marked in ipsilateral dorsal horn of spinal cord (especially in laminae III-IV and contralateral ventromedial medulla (especially in the lateral paragigantocellular reticular nucleus). The results provide evidence in support of the enkephalinergic hypothesis of acupuncture analgesia. It is suggested that increased biosynthesis of enkephalin precursor would help to compensate for the loss of tissue storage of enkephalin during the period of EA stimulation.

Animals↗