Search PubMed⌕ Search

Biomedical subjects

K Shigenobu

Publications and source records attributed to K Shigenobu.

At least 145 records · Page 8Linked to original sources
PubMed1988

Binding of [3H]befunolol to beta-adrenoceptors in cardiac muscles of fetal and neonatal rat.

Characterization of beta-adrenoceptors was studied in heart muscles of rat fetus and neonate. The results of binding assay with [3H]befunolol, a beta-adrenergic partial agonist, to membrane fractions from rat heart muscles indicate that beta-adrenoceptors contain two different affinity sites. In the presence of 5'-guanylylimidodiphosphate, the low affinity site was reduced, while the high affinity site was not affected. The dissociation constants for both sites did not change during pre- and post-natal development. But the maximum binding sites for both sites decreased slightly but significantly (p less than 0.05) during development. A 10-fold decrease in norepinephrine sensitivity and isoprenaline sensitivity during pre- and post-natal development was not explained by the slight decrease in the maximum binding sites.

Adrenergic beta-Antagonists↗
PubMed1988

Changes in sensitivity of rat heart to norepinephrine and isoproterenol during pre- and postnatal development and its relation to sympathetic innervation.

Possible correlation between sympathetic innervation and sensitivity to adrenergic agonists was examined with developing rat hearts. Chronotropic responses of right atria to tyramine (TYR) was absent until the 15th day of gestation. After the 17th day of gestation, the maximum chronotropism by TYR was equal to that by norepinephrine (NE), indicating the development of functional sympathetic innervation to sinus node during this period. In ventricle, TYR responsiveness was low at birth and increased with age, indicating an increased sympathetic innervation during early postnatal period. Both in atria and ventricle, sensitivity to NE was high in early fetal ages followed by a 10-fold decrease after the onset of sympathetic innervation. Similar changes were observed in the sensitivity to isoproterenol, suggesting the postjunctional nature of this sensitivity change. There was no difference in sensitivities to dibutyryl cyclic AMP and forskolin between ventricles from 1-day- and 1-week-old neonates, suggesting changes in beta-receptor-adenylate cyclase system as a cause of this sensitivity change. The observed parallelism between functional sympathetic innervation and postjunctional sensitivity changes supports the hypothesis that sympathetic nerve exerts trophic influence upon cardiac muscle development to regulate the sensitivity to agonists.

Animals↗
PubMed1988

Kinetic analysis of the positive inotropic action (PIA) of ouabain in isolated perfused rabbit heart. Slow onset of PIA and slow binding to Na+, K+-adenosine triphosphatase.

The positive inotropic action (PIA) of ouabain was analyzed kinetically using isolated perfused rabbit heart. The input function of the ouabain concentration in the perfusate (Ci) into the heart was controlled by changing the volume of the reservoir and the rate of ouabain infusion into the reservoir fixed in front of the heart. The time courses of PIA were measured continuously with different infusion rates. The relationship between Ci and PIA clearly depended on the infusion rate in isolated perfused rabbit heart. The binding kinetics of ouabain to Na+, K+-adenosine triphosphatase (ATPase) in the cardiac homogenate showed two kinds of binding sites. The association rate constant (kappa 1), the dissociation rate constant (kappa-1) and the binding capacity of each site was estimated by the simultaneous fitting method. The occupation curve of the high affinity site corresponded well with the PIA measured in the isolated perfused heart at steady state. These results indicate that ouabain binding to the high affinity site is related to the PIA, and the slow binding process of ouabain to Na+, K+-ATPase may be one of the principal reasons for the infusion-rate dependence of ouabain PIA.

Animals↗
PubMed1988

Cardiac effects of ketanserin, a serotonin antagonist--electrophysiological examinations as a part of toxicity studies.

Cardiac effects of ketanserin were examined mainly electrophysiologically with using rat and guinea pig heart muscle preparations. 10(-6)M ketanserin slightly antagonized the positive chronotropic but not inotropic action of serotonin in spontaneously beating guinea pig atria. Ketanserin, only at the concentration as high as 10(-4)M, produced slight rightward shift of the positive chronotropic but not inotropic dose-response curves for norepinephrine in guinea pig atria. In both rat and guinea pig atria, ketanserin per se produced negative chronotropic effect and slight prolongation of action potential duration (APD) at high concentrations, 0.1 or 0.3 mg/ml. In guinea pig ventricular preparation, 1 mg/ml of ketanserin did not affect the rate of rise of the action potential (+Vmax), action potential amplitude and APD. In rat ventricular free wall preparations, 1 mg/ml of ketanserin produced slight increase in APD without affecting the other action potential parameters. In rat ventricular papillary muscle and septum preparations, 0.3 mg/ml of ketanserin tended to produce a decrease in +Vmax and an increase in APD. However, since these changes were produced only at extremely high concentrations and slight in degree, it was concluded that ketanserin does not produce electrophysiological side effects of clinical relevance.

Action Potentials↗
PubMed1987

Contractile response and electrophysiological properties in enzymatically dispersed smooth muscle cells of rat vas deferens.

Electrophysiological studies were performed on single smooth muscle cells isolated from the vas deferens of the rat. The tissue was preincubated in Ca-free modified Tyrode's solution for 1 h and then transferred to a high-K solution for 1 h. It was next minced and treated with the enzyme solution composed of 600-800 unit/ml collagenase and 40 unit/ml elastase. The procedure yielded about 50% spindle shaped Ca-tolerant cells (100-250 microns in length and about 10 microns in diameter). These cells could contract during the superfusion with the solutions containing 10(-8) to 10(-3) M norepinephrine (NE) or adenosine triphosphate (ATP). The cells isolated from the epididymal portion were more sensitive to norepinephrine than were those from the prostatic part. Their basic electrical properties were studied using tight-seal suction electrode technique. The cells had resting potentials around -40 mV and their input resistance was about 0.8 G omega. Action potentials could be evoked by application of depolarizing current. During whole cell voltage clamp, an inward current followed by an outward current was recorded when 800 ms pulses from a holding potential of -60 mV to test potentials positive than -40 mV were applied. The transient outward current generally recorded in other smooth muscle cells was not seen in these cells. The amplitude of the inward current was Ca dependent and sensitive to a Ca antagonist, nicardipine, indicating that Ca ion is the main carrier of this component of the current. When the pipette was filled with Cs-containing solution, the outward current was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Potentiation by bovine serum albumin (BSA) of endothelium-dependent vasodilator response to acetyl glyceryl ether phosphorylcholine (AGEPC).

Endothelium-dependent vasodilator responses of isolated rat aortic strips precontracted with norepinephrine to acetyl glyceryl ether phosphorylcholine (AGEPC) were compared in the presence and absence of bovine serum albumin (BSA). In the absence of BSA, AGEPC produced endothelium-dependent relaxation at concentrations higher than 10(-6) M, which was considered to be non-specific because similar relaxations were produced by other phospholipids (e.g., lysolecithin) at the same concentration range. This non-specific relaxation was suggested to be caused by changes in membrane fluidity of endothelial cells, since high concentrations of AGEPC and other phospholipids were found to produce structural changes in endothelial cells by phase contrast and electron microscopic studies; structural changes were never observed after the application of acetylcholine (ACh). In the presence of BSA (2.5 mg/ml), AGEPC caused endothelium-dependent relaxation at concentrations as low as 10(-9)M; however, relaxations by ACh and lysolecithin were not augmented by the presence of BSA. CV-3988 (10(-5)M), a specific antagonist of AGEPC, inhibited the relaxations by AGEPC in the presence of BSA. From these results, it is suggested that, in the presence of BSA, AGEPC may produce endothelium-dependent relaxation in a specific manner, which is different from the non-specific relaxations observed in the absence of BSA.

Animals↗
PubMed1987

Are alpha-adrenoceptors involved in positive inotropic effects of phenylephrine in chick ventricles?

Effects of phenylephrine on contraction and Ca-action potentials were investigated to clarify whether the alpha-adrenergic mechanism may play a role in chick ventricles. Phenylephrine increased the contractile force of the ventricles isolated from both embryonic and hatched chicks, while methoxamine did not affect their contractility. Developmental changes in the sensitivity to phenylephrine, i.e., increase with age from late embryonic to early neonatal stages, were quite similar to those to a beta-agonist, isoproterenol. The positive inotropism of phenylephrine was antagonized by phentolamine and sotalol, but not antagonized by prazosin or yohimbine. Isobutylmethylxanthine augmented the effect of phenylephrine. Maximum upstroke velocity of Ca-action potentials recorded in partially depolarized ventricles were enhanced by phenylephrine, and the enhancement was eliminated by sotalol but not by phentolamine. The results suggested that the beta-adrenergic action of phenylephrine may be involved in part of its positive inotropic effect, which is mediated by increased Ca-influx through sarcolemma. Another mechanism may also participate in the effects of phenylephrine, but may not necessarily be classified as an "alpha-adrenergic effect".

Animals↗
PubMed1985

Organ culture of young rat vas deferens as an in vitro model for the study of denervation supersensitivity.

To investigate whether organ culture is a suitable in vitro model for studying the mechanisms of denervation-induced supersensitivity, we cultured 1-week-old rat vas deferens for 3 days with a basic applied tension of 20 mg. Cultured muscles showed supersensitivity to norepinephrine and methacholine with concomitant elevation of the maximal response. To compare these changes with those caused by denervation, young rats were chemically denervated by injecting 6-hydroxydopamine, and consequent sensitivity changes were investigated. Denervated muscles showed non-specific supersensitivity to norepinephrine and methacholine but the maximal response did not increase. When these denervated muscles were organ-cultured, they showed no or only a slight increase in sensitivity to norepinephrine and methacholine, but the maximal response increased greatly. These observations led to the suggestion that the increase in sensitivity may be mediated through the same mechanisms as those for denervation supersensitivity. The elevation of the maximal response was suggested to be produced by the improvement of cell-to-cell conduction as well as some other unknown factor(s) probably specific to organ culture. Thus, it was concluded that organ-cultured 1-week-old rat vas deferens is a useful model to study the mechanisms of denervation supersensitivity.

Animals↗
PubMed1985

Acetylcholine supersensitivity in the rat heart produced by neonatal sympathectomy.

Effects of neonatal sympathectomy with antiserum to nerve growth factor or 6-hydroxydopamine on the acetylcholine sensitivity of the rat left atria were investigated. Sensitivities to acetylcholine of atria from immunologically and chemically sympathectomized rats were much higher than that of control at 4 weeks of age. These results suggest possible involvement of the sympathetic nervous system in regulation of cardiac cholinergic sensitivity.

Acetylcholine↗
PubMed1985

Platelet activating factor analogues: lack of correlation between their activities to produce hypotension and endothelium-mediated vasodilation.

Hypotensive activities of 11 synthetic derivatives of platelet activating factor (PAF) were examined and compared with their activities to produce endothelium-related relaxation of isolated rat thoracic aorta. The derivatives showed variety of hypotensive activities; some of the derivatives were more potent than natural PAF and some were virtually inactive compared to PAF. However, all of the compounds tested exhibited exactly the same activities to produce endothelium-related vasodilation. These results confirmed our previous view that the PAF-induced hypotension is not solely due to the endothelium-related vascular relaxation observed in vitro.

Acetylcholine↗
PubMed1985

Effects of oximes, diacetylmonoxime, pyridine-2-aldoxime, and pyridine-2-aldoxime methochloride, on the electrical and mechanical activities of guinea pig cardiac ventricular muscles.

Effects of 3 oximes, diacetylmonoxime (DAM), pyridine-2-aldoxime (PAM) and pyridine-2-aldoxime methochloride (2-PAM), on the normal electrical and mechanical activities and on the slow response action potentials were examined in the guinea pig ventricular muscles. DAM and long-term exposure to high concentrations of PAM produced decreases in contractile force, action potential duration and slow response action potentials, whereas 2-PAM and low concentrations of PAM tended to increase these parameters. Thus, these 3 oximes did not act uniformly on cardiac muscle. It was speculated that DAM and high concentrations of PAM may act as slow channel inhibitors, whereas 2-PAM and low concentrations of PAM may act as slow channel activators.

Action Potentials↗
PubMed1985

TEA prevents the decline of the duration of the action potential in hypoxic cardiac muscle.

Our study was designed to evaluate the effects of the K+ channel blocker tetraethylammonium TEA (20 mM), Ca++ ionophore A23187 (6.9 microM), the Ca++ channel blocker verapamil (2 microM), and CaCl2 (6 mM) on a model of heart damage, hypoxia/reoxygenation of isolated guinea-pig hearts. The right ventricular papillary muscles maintained at 37 degrees C and paced at 60 beats/min were perfused with Ringer solution equilibrated with 95% O2-5% CO2 (normoxia) or 95% N2-5% CO2 (hypoxia). After stabilization of the electrical and mechanical activity, 60 min of hypoxia was induced and then followed by 15 min of reoxygenation. During hypoxia, there was a significant decrease in the action potential duration (APD) and the contractile force (CF). The decrease in APD in the TEA-treated muscle was significantly less than that in the non-treated muscle. However, CF declined at the same rate in both groups. Neither A23187, CaCl2 nor verapamil prevented the decline in both APD and CF. To study the slow responses, the fast Na+ current was first voltage-inactivated by partial depolarization to about -40 mM using an elevated K+ solution. The rate of hypoxia-induced blockade of the slow response was not slower in the presence of 20 mM TEA. These data demonstrate that TEA significantly prevented the decline of APD in hypoxia, but this resistance in APD did not affect the rate of inhibition of mechanical activity.

Action Potentials↗
PubMed1985

Effects of nipradilol (K-351) on alpha-adrenoceptor mediated responses in various isolated tissues.

Nipradilol competitively antagonized norepinephrine- or phenylephrine-induced contractile responses of guinea-pig thoracic aorta. These actions of nipradilol were about 6 times less potent than those of phentolamine. Nitroglycerin showed a non-competitive antagonistic action on norepinephrine-induced contractions of aorta. Furthermore, nipradilol competitively inhibited norepinephrine-induced contractions of rat vas deferens and dose-dependently reduced the phenylephrine-induced inhibitory responses in rabbit ileum. These antagonistic actions of nipradilol were 30 to 100 times less potent than those of phentolamine. Nitroglycerin did not appreciably affect these alpha-adrenoceptor mediated responses in rat vas deferens and rabbit ileum. The inhibitory action of clonidine on the twitch contraction of rat vas deferens produced by intramural stimulation was only slightly antagonized by nipradilol (pA2 = 5.4). Nipradilol and nitroglycerin showed a non-competitive antagonistic action on clonidine-induced contractions of canine saphenous vein after the exposure to phenoxybenzamine, while phentolamine competitively inhibited the clonidine responses. These results suggest that nipradilol possesses an alpha 1-adrenoceptor blocking action; it possesses very weak or practically no presynaptic alpha 2-blocking activity but shows a non-competitive antagonistic action on postsynaptic alpha 2-adrenoceptor mediated contractile responses.

Adrenergic alpha-Antagonists↗