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Biomedical subjects

K Sumikawa

Publications and source records attributed to K Sumikawa.

At least 127 records · Page 7Linked to original sources
PubMed1991

Enhancement by propofol of epinephrine-induced arrhythmias in dogs.

Although propofol is a widely used intravenous anesthetic, its effect on epinephrine-induced arrhythmias remains unknown. This study examined the possible interaction between propofol and epinephrine that might affect the induction of ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with halothane alone, propofol alone, etomidate alone, or etomidate plus varying doses of propofol. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during propofol anesthesia (blood propofol concentration 18.0 +/- 0.98 micrograms/ml) were 2.52 +/- 0.43 micrograms.kg-1.min-1 and 23.6 +/- 8.5 ng/ml, respectively. During halothane anesthesia (end-tidal 1.3 MAC), they were 2.66 +/- 0.21 micrograms.kg-1.min-1 and 35.7 +/- 1.9 ng/ml, respectively. During etomidate anesthesia, they were 9.67 +/- 1.06 micrograms.kg-1.min-1 and 205 +/- 27.5 ng/ml, respectively. The dose-effect relationship for propofol was examined during etomidate plus propofol anesthesia. Propofol reduced the arrhythmogenic plasma concentration of epinephrine in a concentration-dependent manner: at blood propofol concentrations of 2.33 +/- 0.46, 5.46 +/- 0.71, and 11.2 +/- 0.81 micrograms/ml, the corresponding plasma epinephrine concentrations were 182.6 +/- 52.5, 89.0 +/- 28.8, and 26.6 +/- 6.9 ng/ml, respectively. These results suggest that propofol enhances epinephrine-induced arrhythmias in a dose-dependent manner in dogs.

Anesthesia↗
PubMed1991

Pentazocine-induced catecholamine efflux from the dog perfused adrenals.

This study has been undertaken to determine whether pentazocine induces catecholamine efflux from the adrenal medulla as a mechanism for its sympathomimetic effect. Dog isolated adrenals were perfused retrogradely with modified Locke's solution. The efflux of catecholamines from dog perfused adrenals was increased from the resting output of 0.18 +/- 0.04 micrograms min-1 (mean +/- s.e.), to 0.47 +/- 0.13 micrograms min-1 by the administration of pentazocine (50 microM). The pentazocine-induced catecholamine efflux was dose-dependent in the 50-400 microM dose range. This effect of pentazocine was not inhibited by either a combination of atropine and (+)-tubocurarine, or verapamil, in contrast to acetylcholine-induced catecholamine release. There was no significant difference in potency among stereoisomers, i.e. (+)-, (-)- and (+/-)-pentazocine, in inducing catecholamine efflux. Naloxone did not influence the effects of either (+)- or (-)-pentazocine. The interaction of pentazocine with acetylcholine-induced catecholamine release was also examined. Both (+)- and (-)-pentazocine inhibited acetylcholine-induced catecholamine release dose-dependently, and these inhibitory effects were not reversed by naloxone. Acetylcholine-induced catecholamine release was accompanied by increased dopamine-beta-hydroxylase release, whereas pentazocine-induced catecholamine efflux was not. These results suggest that pentazocine directly acts on the adrenal medulla to induce catecholamine efflux via a non-exocytotic mechanism, and that opioid receptors do not play a role in this action.

Acetylcholine↗
PubMed1991

Roles of beta 1- and beta 2-adrenoceptors in the mechanism of halothane myocardial sensitization in dogs.

The authors investigated the comparative roles of beta 1- and beta 2-adrenoceptors in myocardial sensitization by halothane in dogs. The arrhythmogenic dose (AD) of isoproterenol was determined in the presence of various doses of phenylephrine during halothane anesthesia in dogs, and the influences of 1-metoprolol (beta 1-antagonist) and ICI-118,551 (beta 2-antagonist) on the AD were examined. In the presence of 1-metoprolol, the AD of isoproterenol was significantly greater than the control, but in the presence of ICI-118,551, the AD of isoproterenol was lower. Blood pressure during the arrhythmias was higher in the presence of ICI-118,551 than that in controls. In addition, the AD of ritodrine (beta 2-agonist) was also determined at various doses of phenylephrine. The interaction between phenylephrine and ritodrine in inducing arrhythmias showed hyperbolic isoboles. However, 1-metoprolol completely inhibited the occurrence of arrhythmias induced by ritodrine and phenylephrine. The results suggest that myocardial beta 1-adrenoceptors play an essential role in the genesis of arrhythmias during halothane anesthesia in dogs, whereas beta 2-adrenoceptors do not.

Adrenergic beta-Agonists↗
PubMed1991

Contribution of the lungs to the clearance of exogenous dopamine in humans.

The contribution of the lungs to the clearance of exogenous dopamine was analyzed in humans by measuring plasma pulmonary concentrations of dopamine and the pulmonary plasma flow before and after infusion of dopamine. Contribution of the lungs was defined as the ratio between clearance by the lungs and the total plasma clearance of dopamine. Significant transpulmonary gradient of plasma dopamine was observed with infusions at rates of 1.0 and 2.0 micrograms.kg-1.min-1, but not at 0.5 micrograms.kg-1.min-1. The calculated contribution values were 4.90%, 19.23%, and 20.60% at the doses of 0.5, 1.0, and 2.0 micrograms.kg-1.min-1, respectively. The results suggest that the clearance mechanism of the lungs is effective when the plasma dopamine level becomes sufficiently high, and that the lungs clear 19%-21% of clinical doses of dopamine.

Adult↗
PubMed1991

Phenytoin prevents epinephrine-induced arrhythmias through central nervous system in halothane-anesthetized dogs.

The authors investigated the effect of phenytoin through the central nervous system on epinephrine-induced arrhythmias in halothane-anesthetized dogs. The arrhythmogenic dose (AD) of epinephrine during halothane anesthesia was determined in the presence of phenytoin (1 mg/kg), vehicle, and saline, which were administered directly into the cisterna magna. Phenytoin increased the AD of epinephrine as compared with vehicle or saline. The cerebrospinal and plasma concentration of phenytoin during the arrhythmias were 23.6 and less than 0.5 micrograms/ml, respectively. There was no significant difference in AD between the vehicle and saline groups. The same dose of phenytoin (1 mg/kg) administered intravenously did not affect the AD of epinephrine, and the plasma concentration of phenytoin during the arrhythmias was 1.2 micrograms/ml. These findings suggested that phenytoin exerts a protective effect against halothane-epinephrine arrhythmias through a central mechanism and that the central nervous system may be involved, at least in part, in the myocardial sensitization by halothane.

Anesthesia↗
PubMed1990

Regional distribution of mRNA for a putative kainate receptor in rat brain.

A cDNA clone which encodes a putative kainate receptor was prepared with the polymerase chain reaction; from this, 'antisense' RNA fragments were produced and used to evaluate the distribution of mRNA for the kainate-receptor in rat brain with in situ hybridization techniques. The data demonstrate marked regional differences in the abundance of kainate receptor mRNA with highest levels present in the granule and pyramidal cell layers of hippocampus, the Purkinje cell layer of the cerebellum, and all cell layers of the olfactory bulb.

Animals↗
PubMed1990

Differences in phosphatidate hydrolytic activity of human alkaline phosphatase isozymes.

Hydrolytic activities of human alkaline phosphatase isozymes were investigated using phosphatidases with various fatty acyl chains (egg phosphatidate and dioleoyl, distearoyl, dipalmitoyl, dimyristoyl and dilauroyl phosphatidates). In the presence of sodium deoxycholate, purified human placental and intestinal alkaline phosphatases hydrolyzed all the phosphatidates examined. The hydrolytic activity was maximal in the presence of 10 g/l sodium deoxycholate. Of the phosphatidates, dilauroyl phosphatidate was the best substrate. Using the same unit of the enzyme, the phosphatidate hydrolytic activity of placental alkaline phosphatase was 2- to 3-times higher than that of the intestinal enzyme. In contrast, liver alkaline phosphatase did not hydrolyze phosphatidates with long fatty acyl chains (C16-18) even in the presence of sodium deoxycholate. The liver enzyme hydrolyzed dimyristoyl and dilauroyl phosphatidates very slowly. These results show that the phosphatidates with long fatty acyl chains were useful to differentiate placental and intestinal alkaline phosphatases from the liver enzyme, and suggest that the former enzymes play a different physiological role from the liver enzyme.

Alkaline Phosphatase↗
PubMed1990

Levels of mRNA for a putative kainate receptor are affected by seizures.

In situ hybridization and RNA blot-hybridization techniques were used (i) to examine the regional distribution of mRNA for a putative kainate receptor in adult rat brain and ii) to test the possibility that seizures affect expression of the receptor gene. The highest densities of hybridization were distributed within hippocampal pyramidal and granule cells, medial habenula, Purkinje cells and the molecular layer of cerebellum, and olfactory bulb. Recurrent limbic seizures caused a massive, delayed, and reversible reduction in levels of the kainate receptor mRNA in dentate gyrus; lesser decreases were found in pyramidal cell fields of hippocampus and superficial cortex. These findings provide evidence that unusual patterns of physiological activity can alter genomic expression for a subclass of glutamate receptors in brain.

Animals↗
PubMed1989

Inhibition by vecuronium of carbachol-induced influx of 22Na+, 45Ca2+ and secretion of catecholamines in cultured bovine adrenal medullary cells.

In cultured bovine adrenal medullary cells, vecuronium, pancuronium and D-tubocurarine reduced carbachol-induced 45Ca2+ influx and catecholamine secretion by inhibiting 22Na+ influx via nicotinic receptor-ion channel complex with IC50 values of 0.43, 7.6 and 3.9 mumol/l, respectively. IC50 values of pancuronium and D-tubocurarine observed in adrenal medulla were one order of magnitude higher than the plasma concentrations of these muscle relaxants reported to produce 50% neuromuscular blockade, while IC50 of vecuronium was quite close between adrenal medulla and skeletal muscle.

Adrenal Medulla↗
PubMed1989

Assembly and N-glycosylation of all ACh receptor subunits are required for their efficient insertion into plasma membranes.

Various combinations of synthetic acetylcholine receptor (AChR) subunit mRNAs were injected into Xenopus oocytes, and assembly of incomplete AChRs and their insertion into the plasma membrane was studied. Assembly of incomplete AChRs is not greatly affected by the absence of one or two of the other subunits. In contrast, the membrane insertion of incomplete AChRs is profoundly reduced as compared with complete AChRs. The role of N-glycosylation on the assembly of AChR subunits, and on their insertion into plasma membranes, was also studied by using the Xenopus oocyte expression system and tunicamycin. Assembly of non-N-glycosylated AChR subunits occurs in tunicamycin-treated oocytes, but these subunits remain in intracellular compartments, suggesting that N-glycosylation of AChR subunits is not a prerequisite for receptor assembly, but is required for their efficient insertion into the plasma membrane.

Animals↗
PubMed1989

Change in desensitization of cat muscle acetylcholine receptor caused by coexpression of Torpedo acetylcholine receptor subunits in Xenopus oocytes.

Cat muscle acetylcholine receptors (AcChoR) expressed in Xenopus oocytes desensitized more slowly than Torpedo electric organ AcChoRs, also expressed in oocytes. To examine the bases for the different degrees of desensitization, cat-Torpedo AcChoR hybrids were formed by injecting oocytes with cat denervated muscle mRNA mixed with a large excess of cloned Torpedo AcChoR subunit mRNAs. Hybrid AcChoRs formed by coinjection of cat muscle mRNA with the Torpedo beta or delta subunit mRNAs desensitized as slowly as cat AcChoR. In contrast, the hybrid AcChoRs expressed by coinjection with the Torpedo gamma subunit mRNA desensitized much more rapidly than cat AcChoR. The AcChoRs expressed in oocytes injected with cat muscle mRNA together with the Torpedo beta, gamma, and delta subunit mRNAs desensitized as rapidly as Torpedo AcChoR, indicating that the cat alpha subunit does not play an important role in determining the slow rate of desensitization. It is concluded that the difference in the rates of desensitization of cat and Torpedo AcChoRs is determined mainly by differences in their respective gamma subunits.

Animals↗
PubMed1989

Myocardial sensitization by thiopental to arrhythmogenic action of epinephrine in dogs.

This study examined the interaction between thiopental and epinephrine in inducing ventricular arrhythmias in dogs. The arrhythmogenic threshold of epinephrine was determined during anesthesia with either halothane alone, thiopental alone, etomidate plus different doses of thiopental, or halothane plus different doses of thiopental. The arrhythmogenic dose and the corresponding plasma concentration of epinephrine during thiopental anesthesia (plasma thiopental concentration: 46-57 micrograms/ml) were 0.77 +/- 0.04 micrograms.kg-1.min-1 and 10.7 +/- 1.5 ng/ml, respectively. During halothane anesthesia (end-tidal: 1.3 MAC) they were 2.59 +/- 0.49 micrograms.kg-1.min-1 and 45.3 +/- 9.2 ng/ml, respectively. The dose-effect relationship for the thiopental action was examined during etomidate plus thiopental and halothane plus thiopental anesthesia. The arrhythmogenic plasma concentration of epinephrine was inversely proportional to the plasma thiopental concentration during both anesthetics. During etomidate plus thiopental anesthesia, at plasma thiopental concentrations of 0, 11.2 +/- 0.83, 20.1 +/- 1.34, and 33.2 +/- 1.95 micrograms/ml, the corresponding epinephrine concentrations were 201.3 +/- 34.3, 142 +/- 19.5, 69.1 +/- 21.2, and 22.7 +/- 4.5 ng/ml. During halothane plus thiopental anesthesia, at plasma thiopental concentrations of 0, 10 +/- 0.86, 18.3 +/- 0.87, and 31.8 +/- 1.05 micrograms/ml, the corresponding epinephrine concentrations were 45.3 +/- 9.2, 34.6 +/- 8.9, 16.2 +/- 1.74, and 15.1 +/- 1.32 micrograms/ml, respectively. These results suggest that thiopental sensitizes the heart to epinephrine in a dose-dependent manner. This sensitizing action of thiopental would in part explain the thiopental potentiation of hydrocarbon anesthetic-epinephrine arrhythmias.

Anesthetics↗
PubMed1988

Expression of ACh-activated channels and sodium channels by messenger RNAs from innervated and denervated muscle.

Xenopus oocytes were used to express polyadenylated messenger RNAs (mRNAs) encoding acetylcholine receptors and voltage-activated sodium channels from innervated and denervated skeletal muscles of cat and rat. Oocytes injected with mRNA from denervated muscle acquired high sensitivity to acetylcholine, whereas those injected with mRNA from innervated muscle showed virtually no response. Hence the amount of translationally active mRNA encoding acetylcholine receptors appears to be very low in normally innervated muscle, but increases greatly after denervation. Conversely, voltage-activated sodium currents induced by mRNA from innervated muscle were about three times larger than those from denervated muscle; this result suggests that innervated muscle contains more mRNA coding for sodium channels. The sodium current induced by mRNA from denervated muscle was relatively more resistant to block by tetrodotoxin. Thus a proportion of the sodium channels in denervated muscle may be encoded by mRNAs different from those encoding the normal channels.

Acetylcholine↗
PubMed1988

Responses to GABA, glycine and beta-alanine induced in Xenopus oocytes by messenger RNA from chick and rat brain.

Poly (A)+ messenger RNA (mRNA) was extracted from rat and chick brains, and injected into oocytes of Xenopus laevis. This led to the expression of receptors that evoked membrane currents in response to gamma-aminobutyric acid (GABA), glycine and beta-alanine. These currents all inverted at about the chloride equilibrium potential in the oocyte, and showed a marked rectification at negative potentials. Oocytes injected with mRNA from chick optic lobe gave large responses to GABA and beta-alanine, but small responses to glycine. In contrast, one fraction of mRNA from rat cerebral cortex (obtained by sucrose density gradient centrifugation) caused oocytes to develop sensitivity to GABA, glycine and beta-alanine, but very little to GABA. The pharmacological properties of the three amino acid responses also differed. Barbiturate and benzodiazepines potentiated the responses to GABA and beta-alanine, but not to glycine. Strychnine reduced the responses to glycine and beta-alanine, but not to GABA, whereas bicuculline reduced the responses to GABA and beta-alanine, but not to glycine. We conclude that different species of mRNA code for receptors to GABA and glycine, and possibly also for separate beta-alanine receptors.

Amino Acids↗
PubMed1988

Effect of tunicamycin on the expression of functional brain neurotransmitter receptors and voltage-operated channels in Xenopus oocytes.

The role of N-glycosylation on the expression of functional brain neurotransmitter receptors and voltage-operated channels was studied by injecting Xenopus oocytes with mRNA from rat brain or chick optic lobe, and culturing them in the presence or absence of tunicamycin, an inhibitor of asparagine linked glycosylation. Electrophysiological recordings were then made to assess the amounts of functional receptors and channels present in the oocyte membrane. The appearance of gamma-aminobutyric acid (GABA) receptors and voltage-activated Na+ channels was profoundly reduced. In contrast, the functional expression of kainate receptors, and voltage-activated K+ and Ca2+ channels was much less affected. Thus, it seems that kainate receptors, and K+ and Ca2+ channels can be expressed and function normally without being glycosylated. On the other hand, GABA receptors and Na+ channels may need to be N-glycosylated in order to function properly, or to ensure their correct insertion into the membrane.

Amino Acids↗
PubMed1988

Repression of nicotinic acetylcholine receptor expression by antisense RNAs and an oligonucleotide.

Four antisense RNAs, synthesized from cDNA clones coding for the four subunits of the acetylcholine receptor of Torpedo electroplaques, were used to study their effect on the expression of functional Torpedo acetylcholine receptors in Xenopus oocytes. All antisense RNAs inhibited the appearance of functional receptors in the oocyte's surface membrane for at least 1 week. This inhibition was specific because the antisense RNAs did not block the expression of the Cl- channels, also encoded by Torpedo electroplaque mRNA. Experiments with incomplete antisense RNAs and a synthetic oligonucleotide indicate that covering the ribosome binding site or the initiation codon in the mRNA is not a necessary requirement for efficient blocking. Thus, the use of antisense RNAs combined with the Xenopus oocyte system provides a novel approach to screen cDNA libraries for the genes coding for multisubunit neurotransmitter receptors.

Animals↗