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Biomedical subjects

N Satake

Publications and source records attributed to N Satake.

At least 127 records · Page 7Linked to original sources

The inhibitory actions of acebutolol and propranolol on the contractile response to 5-hydroxytryptamine in various isolated vascular smooth muscles.

Pretreatment with acebutolol or propranolol at high concentrations had an inhibitory effect on the contractile response to 5-hydroxytryptamine (5-HT) in most vascular smooth muscles such as rabbit aorta and basilar, mesenteric, renal, femoral arteries and cat coronary artery. The inhibitory actions of both agents were generally greater than on the responses to excess Ca2+ and potassium. In rabbit renal arteries, acebutolol had no effect on the response to 5-HT but inhibited the responses to excess Ca2+ and potassium. Propranolol had a marked inhibitory effect on the response to 5-HT. In all preparations used, the contractions induced by norepinephrine (NE) and histamine showed a much greater resistance to the effect of acebutolol and propranolol than the contractions induced by 5-HT, Ca2+ and potassium. Nifedipine had no inhibitory effect on the response to 5-HT in most of the preparations. Nifedipine inhibited the response to 5-HT only in the basilar arteries. The inhibitory actions of propranolol on the response to 5-HT was greater than that of acebutolol. The inhibitory action of acebutolol and propranolol on the response to 5-HT may be related to mechanisms other than the beta-adrenoceptor blocking action of the drugs. The possible mechanisms of inhibitory action of both beta-adrenoceptor antagonists on 5-HT are discussed.

Acebutolol↗

Alpha 1- and alpha 2-adrenoceptors in the smooth muscle of isolated rabbit urinary bladder and urethra.

The present experiment was undertaken to determine the existence of alpha 1- and alpha 2-adrenoceptors in the smooth muscle of the rabbit bladder dome, trigone and proximal urethra. In the dome pretreated with propranolol (10(-6) M), phenylephrine (10(-5) M-10(-3) M) and norepinephrine (10(-7) M-10(-5) M) caused only a small contraction but norepinephrine, only at high concentrations (10(-4) M-10(-3) M), produced a small relaxation. Clonidine, however, had no effect on the dome. In both trigone and urethra, phenylephrine, clonidine and norepinephrine caused dose-dependent contractions. The contractile response to phenylephrine or norepinephrine was significantly greater than that to clonidine in the trigone but no such difference was observed in the urethra. Prazosin (10(-8) M-10(-6) M, alpha 1-adrenoceptor antagonist) produced a rightward shift of the phenylephrine and clonidine dose-response curve in both the trigone and urethra. Yohimbine (10(-8) M-10(-6) M, alpha 2-adrenoceptor antagonist) inhibited the response to clonidine without significantly affecting the responses to phenylephrine. These studies indicated that alpha 1- and alpha 2-adrenoceptors are present in both the trigone and proximal urethra. In the dome, only alpha 1-adrenoceptors are sparsely distributed.

Adrenergic alpha-Agonists↗

Relaxing effect of nicorandil (N-2-(hydroxyethyl)-nicotinamide nitrate), a new anti-angina agent, on the isolated vascular smooth muscle.

To define the mode of the vasorelaxing action of nicorandil as compared to nitroglycerin, the effects of the agent on the contractile response to various stimulations in rabbit aorta, cat coronary arteries and rabbit basilar arteries were evaluated. Nicorandil had a greater relaxing effect on the maximum response to norepinephrine (NE) than on the potassium (K+) response on all vascular smooth muscles used. In coronary and basilar arteries, however, the inhibitory action of nitroglycerin was not different on the response to both agonists. In coronary and basilar arteries the maximum inhibition of the NE response by nicorandil was greater than that by nitroglycerin. Nicorandil (10(-5) M) but not phentolamine (10(-5) M) inhibited the PGF2 alpha-induced contraction of the aorta. Either nicorandil or nitroglycerin suppressed the response of the aorta to the transmural stimulation. In a Ca2+-free medium containing K+ (40 mM), nicorandil decreased the response to excess Ca2+ in all preparations whereas, nifedipine (10(-6)-10(-5) M) abolished it. Nitroglycerin, however, had no effect on the Ca2+-induced contraction on basilar arteries. In a Ca2+-free medium, the residual NE-induced contraction was inhibited by nicorandil or nitroglycerin but not by nifedipine . The combined treatment with nicorandil and nitroglycerin caused a stronger suppression of residual NE response that that of a single treatment with either agent suggesting the different site of action for the two agents. These results suggest that the mode of vasorelaxing action of nicorandil may be due to the alteration (inhibition) of Ca2+ kinetics in the cell.

Animals↗

Phentolamine-induced rhythmic contractions in bladder detrusor muscle of guinea-pig.

Phentolamine caused a rhythmic contraction concentration-dependently without affecting resting tone in the detrusor muscle. Prazosin, yohimbine, propranolol, noradrenaline, clonidine or isoprenaline failed to cause the rhythmic contraction. These agents did not modify the response to phentolamine suggesting no involvement of alpha- or beta-adrenoceptors in the response to phentolamine. Chlorpheniramine, cimetidine, methysergide, SK&F 83566, atropine, bretylium, hemicholinium or tetrodotoxin failed to inhibit the response to phentolamine. These results suggest that the effect of phentolamine is not mediated through histaminergic, 5-hydroxytryptaminergic, dopaminergic or cholinergic systems, or through transmitter release from nerve endings. Prostaglandin F2 alpha (PGF2 alpha), arachidonic acid but not ATP caused rhythmic contractions which resembled the response to phentolamine. Potassium also caused a contraction with increasing resting tone. Following treatment with nifedipine, or incubation in a Ca2+-free medium, the responses to phentolamine, PGF2 alpha, arachidonic acid and potassium were markedly inhibited or abolished. Cyclo-oxygenase inhibitors such as indomethacin, aspirin and corticosterone inhibited or abolished the responses to phentolamine and arachidonic acid but did not inhibit the response to PGF2 alpha. The results suggest that the phentolamine-induced rhythmic contraction may, at least in part, result from the cyclo-oxygenase metabolite of arachidonic acid in guinea-pig detrusor muscles and a consequent increase in the transmembrane Ca2+-influx.

Animals↗

An alpha-adrenoceptor-blocking action of SGB-483, a new piperazine antihypertensive agent in isolated vascular smooth muscles.

SGB (10(-7)-10(-5) M), a new piperazinyl antihypertensive agent, like prazosin (10(-8)-10(-6) M), a potent preferential alpha 1-adrenoceptor antagonist, inhibited the contractile response of rabbit aorta to norepinephrine and methoxamine in a competitive manner whereas in the cat coronary and rabbit basilar artery, the inhibition by SGB was not a competitive one. The potency of the inhibitory action of SGB was less than that of prazosin in all preparations used. Neither SGB nor prazosin had any inhibitory effect on the response to potassium, 5-hydroxytryptamine, prostaglandin F2 alpha, and excess Ca2+ in all preparations. In the rabbit aortic membrane preparation, the specific binding of [3H]-prazosin was inhibited, concentration-dependently, by SGB with IC50 value of 1.4 +/- 0.09 microM. These studies indicated that SGB has an alpha 1-adrenoceptor-blocking action though its potency is weaker than prazosin.

Adrenergic alpha-Antagonists↗

Palytoxin isolated from marine coelenterates. The inhibitory action on (Na,K)-ATPase.

Palytoxin (PTX), C129H223N3O54, a highly toxic substance isolated from zoanthids of Palythoa tuberculosa, inhibited (Na,K)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) prepared from guinea pig heart and hog cerebral cortex in a dose-dependent manner at concentrations greater than 10(-8) M. In the presence of Na (100 mM) and K (20 mM), PTX showed potency nearly equal to that of ouabain. When the ATPase was activated by the various Na concentrations at a constant K concentration, both PTX and ouabain inhibited the ATPase activity noncompetitively. On the other hand, when K concentration was changed at a constant Na concentration, PTX caused a competitive inhibition in all ranges of K concentrations employed, whereas ouabain caused a competitive inhibition at low concentrations and a noncompetitive inhibition at high concentrations.

Acrylamides↗

The inhibitory action of FR 34235 (a new Ca2+ entry blocker) as compared to nimodipine and nifedipine on the contractile response to norepinephrine, potassium and 5-hydroxytryptamine in rabbit basilar artery.

In isolated basilar arteries, FR 34235 (FR), a new Ca2+ entry blocker, inhibited the contractile response to potassium, norepinephrine and 5-hydroxytryptamine (5-HT) in a dose-dependent manner. The potency of the inhibitory action of FR was in the following order: potassium greater than 5-HT greater than norepinephrine. Nifedipine had a similar inhibitory action on the responses. Nimodipine had no inhibitory effect on the response to norepinephrine but suppressed the responses to potassium and 5-HT.

Animals↗

Active electrogenic mechanisms for alkali and acid transport in turtle bladders.

Immediately after mounting in the Ussing chamber between choline bicarbonate Ringer solutions devoid of exogenous Na and Cl, the serosal fluid is electronegative to the luminal fluid in bladders from postabsorptive and acidotic turtles; and electropositive in bladders from alkalotic turtles. In bladders from postprandial turtles, the electrical orientation, initially serosal positive, reverses to serosal negative. Serosal additions of 3-isobutyl-1-methylxanthine (IBMX) and adenosine 3',5'-cyclic monophosphate (cAMP) produce no changes in the negative short-circuiting current (Isc) of acidotic turtles but induce large positively-directed increases of Isc in bladders from other turtle groups. With IBMX and cAMP in the (HCO3 + CO2)-rich serosal fluid at pH 7.2 and with luminal pH maintained at 4.0-5.0, the rate at which titratable alkali enters the luminal fluid is electrochemically equal to the positive Isc; and this increased positive Isc is the same as that in the absence of transepithelial gradients. The effects of acetazolamide and 4-acetamido-4-isothiocyanostilbene-2,2'-disulfonic acid on positive and negative Isc are presented. It is concluded that isolated bladders from alkalotic, postprandial or postabsorptive turtles, but not those from acidotic turtles, possess an active electrogenic mechanism for a Na-independent Cl-independent secretion of bicarbonate. This transport process is accelerated by phosphodiesterase inhibitors (IBMX) and cAMP or its eight substituted derivatives.

1-Methyl-3-isobutylxanthine↗

Effect of S-adenosylhomocystein on color avoidance behavior.

The intracranial injection of an inhibitor of the enzyme hydroxyindole-O-methyltransferase (S-adenosylhomocystein: SAH) in goldfish prior to color avoidance training caused delay in responding to either white or green conditioned stimulus in the shuttlebox. Latency of the responses to red or blue conditioned stimulus was not affected by an injection of SAH. The results suggested that an injection of SAH increased the preference to white and green color, but did not increase the general brightness preference.

Animals↗

Effect of methionine-enkephalin on xanthopore aggregation.

The intracranial injection of an opioid antagonist (naloxone) caused aggregation of xanthophores in goldfish scales. This aggregating effect produced by naloxone was inhibited by an injection of methionine-enkephalin (M-ENK). M-ENK, when injected together with melatonin which normally produces aggregation of xanthophores, interfered with the effect of melatonin by inhibiting the aggregation. An injection of naloxone together with melatonin showed no difference in the aggregation from that of either naloxone or melatonin alone. The possibility of interaction between melatonin and M-ENK was discussed.

Animals↗

General properties of antimony microelectrode in comparison with glass microelectrode for pH measurement.

Two kinds of pH-sensitive microelectrodes were constructed: 1) glass microelectrode with a pH-sensitive tip of 50--100 micrometers in length, and 2) antimony (Sb) microelectrode with a tip of 1--5 micrometers in outside diameter. Comparisons of the two were made on the change in the electromotive force (EMF) in response to various pHs and biological applicability. The pH sensitivity (slope constant) at 20 degrees C of the glass and Sb-microelectrodes averaged 51.7 and 51.9 (-mV/pH), respectively. Over the pH range of 2 to 9, both electrodes responded linearly to the change of pH. The pH-dependent EMF of the Sb-microelectrode was influenced by phosphate buffers, but not by Tris-HCl buffers. Through the glass microelectrode showed a linear response to all the buffers tested, its slope constant tended to be limited by the surface area of the pH-sensitive tip. The stability of the EMFs was well within 1 mV for 12 hr with the glass microelectrode but more than 10 mV with the Sb-microelectrode. One the other hand, the 95% response time was about 1 min with the glass microelectrode, whereas it was less than a few seconds with the Sb-microelectrode. Blood pH was measured with the two electrodes and reasonable values were obtained with both methods, although the values by use of the Sb-microelectrode were slightly higher than those of the other. In view of the practical ease of manufacturing, maintenance and durability, the use of the Sb-microelectrode in biological measurement should also be re-evaluated, but several restrictions must be imposed on it.

Animals↗

Physicochemical characteristics of antimony microelectrode with special reference to selection of standard buffers.

1) Antimony (Sb) microelectrodes with tips of 2 to 5 micrometers in outside diameter were constructed, and their electromotive forces (EMF) were tested in response to the pH of several calibration buffers. The data were compared with those of glass pH electrodes. 2) Increasing ionic strength (I) caused a significant deviation in pH readings of the Sb-microelectrode (delta pHSb-Glass). The above salt effect was empirically given by delta pHSb-Glass = 0.017--0.125 I (I = 0.09--0.22) 3) Even with the correction for ionic strength, the values of delta pHSb-Glass were still dependent on the nature of calibration buffers employed. Among various buffers, Tris buffer [Tris(hydroxymethyl)-aminomethane, (THAM)] had the least disturbance on the Sb-microelectrode, and bicarbonate had also relatively minor effect. 4) The pH value according to the Sb-electrode was caused to deviate considerably by phosphate. The effect of phosphate within the range of 1 to 67 mM can be predicted by 1/delta pHSb-Glass = 1 + (0.174/[PO4]) 5) Like phosphates, BES [N, N-Bis (2-hydroxyethyl)-2-aminoethane sulfonic acid] also had a significant effect on the EMF of the Sb-microelectrode. 6) Upon consideration of the above facts, measurements of several biological fluids, such as those of the in vivo pH of intratubular fluid of bullfrog kidney were carried out with the Sb-microelectrode calibrated by 90 mM Tris buffer. 7) Thus, it was concluded that the Sb-microelectrode when properly calibrated could be used for the pH measurement of ultraminute amounts of biological samples.

Animals↗

Temperature coefficient of and oxygen effect on the antimony microelectrode.

With regard to pH measurement of biological fluids in vivo with metal-metal oxide microelectrodes, the effect of temperature and partial pressure of oxygen on antimony (Sb) microelectrodes was examined, and pH of blood was estimated in the bullfrog. The temperature coefficient (dE/dt) of electromotive force (EMF) of Sb-microelectrodes in the range of 7 to 37 degrees C was -1.18 +/- 0.113 mV/degrees C (mean +/- SEM) in Ringer solution, whereas that of the pH glass electrode in the same solution was -0.43 +/- 0.035 mV/degrees C. When estimated in Tris buffer solution, it was -0.06 +/- 0.063 mV/degrees C for Sb-microelectrodes and 1.05 + 0.036 mV/degrees C for glass electrodes. The change of slope constant (alpha in -mV/pH) in the Sb-microelectrode due to temperature change could be predicted empirically from: alpha = 0.40 (t-25) + 55.3, where t represents the measuring temperature in degrees C. The resultant deviation of pH reading between Sb and glass electrodes, delta pHSb-Glass, may be expressed by: delta pHSb-Glass = 0.00183 (t-25) +0.016. In the range of 45 to 760 mmHg of oxygen partial pressure it fixed pH, the EMF increased linearly with the increase of Po2, the slope (dE/dlog(Po2)) being 11.7 +/- 0.42 (SEM) mV (n = 13, t = 25 degrees C). In consideration of the above effects, the blood pH of bullfrog was estimated to be 7.697 +/- 0.092 (SD) and 7.729 +/- 0.111 with glass and Sb-microelectrodes respectively, the difference between the two being relatively minor.

Animals↗