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Biomedical subjects

S Komori

Publications and source records attributed to S Komori.

At least 163 records · Page 9Linked to original sources
PubMed1988

Some membrane properties of the circular muscle of chicken rectum and its non-adrenergic non-cholinergic innervation.

1. Membrane properties and innervation of the circular muscle of chicken rectum were investigated by recording intracellularly electrotonic potentials evoked by passing current, and excitatory and inhibitory junction potentials (EJPs and IJPs) evoked by electrical stimulation of the extrinsic or intrinsic nerves. 2. The membrane potential was -55 +/- 0.6 mV (n = 95). Action potentials of long duration (1.2-4.0 s) discharged spontaneously, or were generated when the membrane depolarization due to either electrotonic potential or EJP reached the threshold. The drug D600 blocked the generation of action potentials. 3. Electrotonic potentials spread fairly well in the longitudinal direction of the muscle fibres but not in the transverse direction. The longitudinal space constant was 1.7 +/- 0.2 mm (n = 10) and the membrane time constant was 205 +/- 21 ms (n = 10). 4. Field stimulation of intramural nerves evoked an EJP followed by a long-lasting IJP (3-12 s in total duration) in most cells, and an EJP alone or an IJP alone in a small number of cells. The EJP and IJP were preserved in the simultaneous presence of atropine and guanethidine, but abolished with tetrodotoxin. 5. Stimulation of Remak's nerve trunk or its branches produced EJPs which were atropine resistant and guanethidine resistant just like the EJP elicited by intramural nerve stimulation. The extrinsic nerve stimulation was ineffective in eliciting IJPs. 6. The EJP amplitude declined in a linear manner as the distance from the stimulating site of intramural nerves was increased. The decline was much greater along the transverse axis than the longitudinal axis of circular muscle fibres. 7. The reversal potential for the EJP was estimated by extrapolation to be about - 15.3 +/- 0.3 mV (n = 7). 8. Apamin did not inhibit the IJP. During the hyperpolarization of a single IJP or summed IJPs, electrotonic potentials remained unchanged or slightly decreased in amplitude.

Action Potentials↗
PubMed1988

Production of heavy-chain class-switch variants of human monoclonal antibody by recombinant DNA technology.

We have previously established a human-mouse heterohybridoma (H6-3C4), which produced a human sperm-immobilizing antibody (mu, lambda of human type). The human rearranged immunoglobulin mu-chain and lambda-chain genes were cloned from the hybridoma H6-3C4. The cloned V region of the heavy chain (VH) gene was ligated to human immunoglobulin gamma 1-heavy chain constant region (C gamma 1) genes. This resulted in the heavy-chain class-switch from mu-chain to gamma 1-chain of H6-3C4 antibody. The class-switched heavy-chain gene as well as the cloned lambda-chain gene were introduced into mouse myeloma cell line X63Ag8.653 by protoplast fusion and electroporation. The stable transformants produced the human IgG monoclonal antibody, which fully retained specificity to human sperm cells and sperm-immobilizing activity.

Animals↗
PubMed1987

Complementary DNA for a human subgroup IV immunoglobulin lambda-chain.

We have cloned a cDNA (p3C4 lambda 5) encoding a human immunoglobulin lambda-chain of human-mouse heterohybridoma, H6-3C4, which produces a human monoclonal antibody against human sperm surface antigen. Amino acid sequence deduced from the nucleotide sequence of V lambda (V lambda 3C4) of cloned cDNA was closely related to that of SHV lambda protein, a member of subgroup IV. Southern blot analysis of human genomic DNAs by using V lambda 3C4 as a probe detected at least 8 cross-hybridizing members of subgroup V lambda IV. Restriction enzyme fragment polymorphism (RFLP) appeared to be present in normal individuals with V lambda 3C4 gene.

Amino Acid Sequence↗
PubMed1987

Nerve pathways involved in adrenergic regulation of electrical and mechanical activities in the chicken rectum.

Peripheral nerve pathways responsible for adrenergic inhibition of mechanical and electrical activities in the chicken rectum and receptors mediating the adrenergic inhibition were investigated in isolated extrinsically-innervated rectum of the chicken. Electrical stimulation of the anal end (Ra) or the ileal cut end (Ri) of Remak's nerve, or perivascular nerves (P) elicited relaxation of the rectum pretreated with atropine (0.5 microM) and hexamethonium (0.3 mM) to block the cholinergic and non-cholinergic, non-adrenergic excitatory innervations. Ri stimulation was much less effective than Ra and P stimulations. The relaxation was shown to be related to cessation of spontaneous spike discharge of the longitudinal muscle which was accompanied by membrane hyperpolarization. The inhibitory effects elicited by Ra and P stimulations, which were prolonged beyond the period of the stimulation, were converted to transient ones by propranolol (3.4 microM). Phentolamine (2.6 microM) reduced effectively the residual effects. In contrast, the effects of Ri stimulation were little affected by these drugs. The present results provide evidence for the existence of two nerve pathways responsible for direct adrenergic inhibitory innervation to the chicken rectum, one running orally in Remak's nerve trunk, leaving it and descending in the branches to the rectum, and the other running as the perivascular nerves along the arterial supplies of the rectum. The direct innervation is mediated predominantly by beta-adrenoceptors.

Animals↗
PubMed1987

Do antiarrhythmic drugs act on the site of abnormal impulse generation or act on the normal myocardium?

Locally-induced digitalis arrhythmia was produced to study whether antiarrhythmic drugs suppress arrhythmia by directly acting on the abnormal impulse generation or by suppressing Na channels of normal myocardium to make it unresponsive to abnormal impulses. Dogs were thoractomized and the anterior descending artery (ADA) was isolated and autoperfused with arterial blood from the carotid artery. Forty micrograms and an additional 10 micrograms every 20 min of ouabain was injected directly into the ADA produced ventricular tachycardia originating from the digitalis intoxication. Locally injected class 1 antiarrhythmic drugs, including tetrodotoxin, were effective in suppressing this arrhythmia. However, when intravenously applied lidocaine was prevented from reaching the ADA area, lidocaine was not effective in suppressing this arrhythmia. We conclude that class 1 drugs produce antiarrhythmic effect by directly suppressing the digitalis toxicated area, not by suppressing the normal myocardium.

Animals↗
PubMed1987

The amino acid sequence of a smooth muscle-contracting peptide from chicken rectum. Identity to chicken neurotensin.

Previous studies have demonstrated that chicken rectum contains a peptide which exerts a potent, excitatory action on the smooth muscle of chicken rectum, and this peptide is most likely to be chicken neurotensin isolated recently from chicken small intestine. In the present study, the peptide was extracted from 2 kg of chicken rectums, and then it was isolated by gel filtration, ion exchange chromatography, high voltage paper electrophoresis and HPLC. Amino acid analysis of the peptide revealed that it is a tridecapeptide composed of aspartic acid (Asp), glutamic acid (Glu), proline (Pro), alanine (Ala), valine (Val), isoleucine (Ile), two residues of leucine (Leu), tyrosine (Tyr), histidine (His), lysine (Lys) and two residues of arginine (Arg). Its amino acid sequence was determined to be pGlu-Leu-His-Val-Asn-Lys-Ala-Arg-Arg-Pro-Tyr-Ile-Leu-OH. The molecule is identical to chicken neurotensin.

Amino Acid Sequence↗
PubMed1986

Smooth muscle excitatory substances from Remak nerve of the chicken and a comparison of their pharmacological and chemical properties with substance P.

Active substances extracted from the Remak nerve of the chicken were subjected to chromatographic and electrophoretic separation followed by bioassay of contracting activities on the longitudinal muscle of the guinea-pig ileum (LMGPI) and on the isolated whole chick rectum (WCR). Gel filtration profiles on a Sephadex G-50 column showed two peaks of LMGPI-contracting activity and of WCR-contracting activity. No difference was seen in the enzymatic destruction between the LMGPI-contracting activity and substance P. Their similarities were also indicated by the parallelism of their elution curves in the gel chromatography on Sephadex G-25, their equal stability in acid solutions, and comparable antagonism and inhibition of the contractile effects on LMGPI by substance P antagonists and after desensitization of substance P receptors. Ion exchange chromatography revealed the existence of two main substances responsible for the LMGPI-contracting activity. One of them eluted at the same position as that for substance P, but differed in immunoreactivity and electrophoretic mobility from substance P. The WCR-contracting activity differed from the LMGPI-contracting activity in that it was pepsin-resistant and carboxypeptidase A-susceptible, and it eluted at a different position during ion exchange chromatography. It seems likely that the LMGPI-contracting activity in the extracts is attributed to a substance P-family of peptides, but the WCR-contracting activity is due to another substance of a peptide nature.

Animals↗
PubMed1986

Isolation of smooth muscle excitatory substances from chicken rectum and their characterization.

Acid-acetone extracts of the chicken rectum were subjected to chromatographic and electrophoretic separation, and two new smooth muscle-contracting substances close to purity were obtained. One of them showed chemical and biological characteristics similar to those of substance P, but it was clearly different from substance P on the basis of chromatographic and electrophoretic criteria. Thus, one could be a peptide belonging to the substance P-family. The other substance was also shown to be of peptide nature since its biological activity was destroyed by chymotrypsin and carboxypeptidase A. Parallel bioassay on the two tissues of the longitudinal muscle of the guinea-pig ileum and the isolated whole chick rectum revealed that none of the peptides such as substance P, physalaemin, kassinin, eledoisin, bradykinin and angiotensin II could be a candidate for the active substance. The biological activity was not antagonized by naloxone, suggesting that the substance was a peptide other than the opioid compounds. The molecular sizes estimated by gel filtration are 1300 for the substance P-like peptide and 1600 for the other substance. The possible physiological roles of the two substances as an excitatory non-adrenergic, non-cholinergic transmitter were discussed.

Animals↗
PubMed1986

Isolation of a peptide material showing strong rectal muscle-contracting activity from chicken rectum and its identification as chicken neurotensin.

A peptide with strong activity to contract isolated whole chick rectum, RC-substance, in an acid-acetone extract prepared from 2.0 kg wet weight of chicken rectums was isolated by gel filtration on Sephadex G-25, ion exchange chromatography on a SP-Sephadex C-25 column, and high voltage paper chromatography. The close purity of this substance was established by high performance liquid chromatography (HPLC). The RC-substance displayed the same pharmacological and enzymatic properties as bovine neurotensin (NT). However, it differed from bovine NT in its behavior during the ion exchange chromatography, in its mobility during the electrophoresis, and in its retention time on HPLC. The amino acid analysis by a conventional OPA method revealed that all ten amino acid residues of which molar ratios were integral were common with those of chicken NT. Its biological activities were equipotent to those of bovine NT, suggesting the presence of proline in the COOH-terminal hexapeptide. From these results, it can be concluded that the RC-substance is identical to chicken NT. Exposure to high concentrations of bovine NT rendered the rectal smooth muscle of the chicken insensitive to subsequent applications of the RC-substance as well as bovine NT. This desensitization also reduced specifically the contractile responses of the rectal muscle elicited by non-adrenergic and non-cholinergic (NANC) nerve stimulation, suggesting a possible physiological role of the RC-substance as the neurotransmitter of NANC neurones.

Amino Acids↗
PubMed1985

Canine digitalis arrhythmia as a model for detecting Na-channel blocking antiarrhythmic drugs: a comparative study using other canine arrhythmia models and the new antiarrhythmic drugs, propafenone, tocainide, and SUN 1165.

Antiarrhythmic effects of three new drugs, propafenone, tocainide, and SUN 1165, were examined using three canine ventricular arrhythmia models, i.e., digitalis, adrenaline and two-stage coronary ligation arrhythmias. The effects of procainamide, disopyramide, lidocaine, and phenytoin, class 1 antiarrhythmic drugs, on digitalis arrhythmia were also examined. The minimum effective plasma concentrations of all these drugs for each arrhythmia model were determined for a quantitative comparison. Propafenone and tocainide suppressed all the arrhythmias, while SUN 1165 suppressed digitalis and coronary ligation arrhythmias. The minimum effective plasma concentrations of propafenone for digitalis, adrenaline, 24-h coronary ligation, and 48-h coronary ligation arrhythmias were 1.8 +/- 0.7, 0.58 +/- 0.20, 3.5 +/- 0.3, and 3.6 +/- 0.9 micrograms/ml, respectively, and those of tocainide were 6.2 +/- 2.1, 23.7 +/- 9.0, 11.4 +/- 0.5, and 8.6 +/- 2.9 micrograms/ml, respectively (mean +/- standard deviation, n = 6-7). The minimum effective concentrations of SUN 1165 for digitalis, 24-h coronary ligation, and 48-h coronary ligation arrhythmias were 0.92 +/- 0.19, 2.5 +/- 0.4, and 1.2 +/- 0.4 micrograms/ml. The minimum effective concentrations for digitalis arrhythmias were 1.7 +/- 0.4 micrograms/ml for disopyramide, 10.1 +/- 2.4 micrograms/ml for procainamide, 3.5 +/- 1.6 micrograms/ml for lidocaine, and 11.3 +/- 3.0 micrograms/ml for phenytoin. Digitalis arrhythmia seems to be a useful model for detecting class 1 drugs, as it was suppressed by all the class 1 Na-channel blocking antiarrhythmic drugs, while class 2 beta adrenergic blockers and class 4 Ca-channel blockers had no effect. Also, not all the class 1 drugs suppressed coronary ligation and adrenaline arrhythmias.

Animals↗
PubMed1985

Antiarrhythmic effects of coronary vasodilators on canine ventricular arrhythmia models.

Antiarrhythmic effects of intravenous coronary vasodilators (verapamil, diltiazem, bepridil, trimetazidine and nicorandil) were evaluated using two canine ventricular arrhythmia models (halothane-adrenaline arrhythmia and digitalis arrhythmia), and the minimum effective plasma concentrations of the drugs were determined for each arrhythmia model. Verapamil (0.1 mg/kg), diltiazem (0.1 mg/kg), bepridil (1 mg/kg) and high dose trimetazidine (10 mg/kg) were effective on halothane-adrenaline arrhythmia; and the minimum effective plasma concentrations of the above drugs were less than 30 +/- 10 ng/ml, less than 18 +/- 5 ng/ml, 0.38 +/- 0.11 microgram/ml and 7.0 +/- 1.5 micrograms/ml, respectively. Nicorandil (1 mg/kg) did not suppress halothane-adrenaline arrhythmia. Verapamil, diltiazem and bepridil must have suppressed the halothane-adrenaline arrhythmia by blocking the Ca channel. Verapamil (1 mg/kg), diltiazem (1 mg/kg), bepridil (5 mg/kg), trimetazidine (3 mg/kg) and nicorandil (3 mg/kg) were ineffective on digitalis arrhythmia, even though their maximum hypotensive doses were used.

Animals↗
PubMed1984

Presynaptic, muscarinic inhibition of non-adrenergic, non-cholinergic neuromuscular transmission in the chicken rectum.

Cholinergic inhibition of the non-adrenergic, non-cholinergic ( NANC ) transmission was investigated in the chicken isolated rectum with Remak's nerve attached. Stimulation of Remak's nerve (RT stimulation) at frequencies higher than 5 Hz elicited a late, slow contraction of the rectum in addition to an initial, fast NANC contraction. The late, slow contraction was blocked by atropine (0.25 microgram ml-1), potentiated by physostigmine (50 ng ml-1) and accompanied by an overflow of acetylcholine into the vascular perfusate, indicating the existence of cholinergic innervation to the rectum via Remak's nerve. RT stimulation (10 pulses at 0.5-1.0 Hz) elicited NANC -mediated excitatory junction potentials (e.j.ps). The e.j.p. amplitude declined at the second stimulus and then increased to reach a plateau. Atropine, by abolishing this decrease in amplitude, increased the mean amplitude of the e.j.ps during trains of stimuli but atropine did not affect the amplitude of the first e.j.p. Physostigmine reduced the mean e.j.p. amplitude, and this action was readily antagonized by atropine. A single intramural nerve stimulation delivered 2s or less before RT stimulation with trains of stimuli, suppressed the amplitude of the first e.j.p. of the train. This effect was abolished by atropine. Atropine in concentrations high enough to affect the e.j.p. amplitude had no effect on the resting membrane potential, the threshold for generating an action potential, or membrane resistance of the smooth muscle. It is concluded that RT stimulation at low frequencies causes the release of acetylcholine simultaneously with the NANC transmitter. The released acetylcholine acts mainly on prejunctional muscarinic receptors and mediates an inhibitory effect on the release of the NANC transmitter.

Acetylcholine↗
PubMed1984

Cholinergic inhibition of adrenergic transmission in the dog retractor penis muscle.

Muscarinic, cholinergic depression of adrenergic excitatory transmission was investigated by the microelectrode method in isolated dog retractor penis muscle. Electrical stimulation of the intramural nerves with single or repetitive stimuli elicited adrenergic contractions and excitatory junction potentials (e.j.p.s). The mechanical response and e.j.p. were suppressed by physostigmine (5 x 10(-7) g/ml) and carbachol (up to 5 x 10(-8) g/ml) without changing the sensitivity of the muscle to noradrenaline and muscle membrane resistance measured by electrotonic potentials. Atropine reversed the drug-induced attenuation of these responses, but atropine itself had no effect on them. Carbachol at 5 x 10(-8) g/ml, where the e.j.p. was blocked, caused a depolarization of the muscle membrane (less than 5 mV), whereas the same extent of depolarization produced by high K solution resulted in only a small decrease in e.j.p. amplitude. These results suggest that excitatory adrenergic transmission in the dog retractor penis muscle is depressed prejunctionally by a cholinergic mechanism.

Animals↗
PubMed1984

A smooth muscle excitatory material from the nerve of Remak of the chicken rectum.

The chicken rectum receives a powerful excitatory innervation of nonadrenergic, non-cholinergic (NANC) nerves via the Remak nerve which is a ganglionated nerve trunk in the fowl vicera. To extract a smooth muscle excitatory material from the Remak nerve, tissue samples were boiled in 0.01 N HCl at 100 degrees C for 5-7 min, homogenized, and centrifuged. Aliquots of supernatant were defatted with petroleum ether and lyophilized. The lyophilized residue dissolved in water (ERN) was bioassayed for contracting activity on the longitudinal muscle of the guinea-pig ileum and, if needed, the isolated whole chick rectum. Approximately half of the contacting activity of ERN was attributable to acetylcholine. The remainder was found to be mediated by neither histamine, serotonin, angiotensin II nor prostaglandins (E1, E2 and F2 alpha). The ERN activity was abolished by 2-3 min boiling in alkali and 30 min incubation at 37 degrees C with pepsin, but sustained after boiling in acid, indicating that the mediator of the contracting activity is probably a peptide. Active fractions were obtained with one peak after gel filtration with Sephadex G-50. They were pooled and applied to a Sephadex G-25 column. The Ve/Vo values for the active material ranged from 1.69 to 1.85, indicating that it has a molecular weight of 1000-1300 by comparison with Ve/Vo values for peptides of known molecular weights applied to the same column.

Adenosine Triphosphate↗
PubMed1984

[Effects of N-696, a new beta-blocking agent, on canine experimental arrhythmias].

We evaluated antiarrhythmic effects of N-696 using canine digitalis ventricular arrhythmia models and electrophysiological actions of N-696 using canine ventricular muscles and isolated blood perfused A-V node preparations and compared the effects with those of propranolol. 1) N-696 at 30 mg/kg, i.v. was not effective on digitalis arrhythmia, but reduced the total heart rate and atrial rate for 60 min and transiently decreased the blood pressure. Propranolol at 3 mg/kg, i.v. transiently suppressed digitalis ventricular arrhythmia and decreased the total heart rate, atrial rate and blood pressure. The minimum effective plasma concentration of propranolol was 1.7 +/- 0.4 microgram/ml. 2) Ten to 100 micrograms/ml N-696 and 3 to 10 micrograms/ml propranolol did not affect the resting potential and the action potential duration at 75% repolarization of the canine ventricular muscle, but decreased the maximum rate of rise of the action potential in a dose-dependent fashion, and 100 micrograms/ml N-696 decreased significantly the action potential amplitude. The minimum effective drug concentration of N-696 was 60 micrograms/ml, and that of propranolol was 6 micrograms/ml. 3) N-696 (30 micrograms-3mg) dose-dependently delayed the A-V conduction time of the isolated blood perfused A-V node preparation when it was administered into the posterior septal artery (PSA) and the anterior septal artery (ASA). Propranolol (10-600 micrograms) also had similar effects, but the doses of N-696 delaying the A-V conduction time by 15% was about 8 to 21 times higher than those of propranolol.

Adrenergic beta-Antagonists↗