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Y Kitada

Publications and source records attributed to Y Kitada.

At least 37 records · Page 2Linked to original sources
PubMed1995

Anions modulate cation-induced responses of single units of the frog glossopharyngeal nerve.

Fibers of the frog glossopharyngeal nerve that are sensitive to water stimulation also respond to Ca, Mg and Na salts. During stimulation with a salt, the cation and the anion are applied together and the anion could influence the response to the cation. We examined this interaction using single unit recordings at the level of fungiform papilla. Nerve impulses of large amplitude were recorded in response to the stimulation of adjacent papillae with increasing concentrations of various Ca, Mg and Na salts. For a given cation, the elicited spike frequency depended on the anion. For example, the responses of single fibers to Ca2+ concentrations above 0.1 mM were maximal with CaSO4 and minimal with Ca(SCN)2. The rank order of efficiency was CaSO4 > CaCl2 = CaBr2 = Ca(NO3)2 > Ca(SCN)2 for Ca2+ ions at 5 mM. The effects of these anions were reversed for Mg and Na salts, the rank orders being Mg(SCN)2 > Mg(NO3)2 > MgBr2 = MgCl2 > MgSO4, for Mg2+ ions at 200 mM, and NaSCN > NaI > NaNO3 > NaBr > NaCl >> NaF = Na2SO4, for Na+ ions at 500 mM. All these sequences correspond to the lyotropic rank order of the anions. In stimulation by a mixture of Ca and Na salts, which have different rank orders with respect to anions, either the response to Ca2+ ions or the response to Na+ ions could be eliminated as a result of mutual antagonism between Ca2+ and Na+ ions. In this case, the rank order of anions was dependent only on the cation that was able to exert a stimulatory effect in the mixture. Threshold concentrations for Ca, Mg and Na salts are influenced by cationic properties, but not by anionic properties. We hypothesize that anions can modulate the efficacy of cation transduction by binding to a membrane element that interacts with each of the three distinct receptors for Ca2+, Mg2+ and Na+ ions without altering the affinities of these receptors for the respective cations. The present results cannot be interpreted in terms of permeability of the apical membrane to anions and changes in surface potential on the apical membrane. The possibility is discussed that an anion-selective paracellular pathway between taste cells is responsible for the effect of anions on the cation-induced response.

Animals↗
PubMed1995

Effect of a calcium-sensitizing positive inotropic agent MCI-154 and its combined use with enalapril on postischemic contractile dysfunction of dog hearts.

We wished to elucidate the effects of the calcium-sensitizing positive inotropic agent MCI-154 and its combined use with an angiotensin-converting enzyme (ACE) inhibitor enalapril on postischemic contractile dysfunction. Anesthetized dogs underwent a 30-min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusion. Regional myocardial segment shortening in the ischemic LAD area was assessed by sonomicrometry. Myocardial segment shortening decreased in response to the LAD occlusion and remained decreased during 2-h reperfusion. The intravenous infusion of MCI-154 (0.1 or 0.3 micrograms/kg/min) initiated 10 min after occlusion and throughout reperfusion significantly improved the recovery of segment shortening. The alleviation of the postischemic contractile dysfunction by MCI-154 was augmented when the animals were treated with a bous injection of enalapril (0.3 mg/kg) 15 min before ischemia followed by an infusion of the drug (0.003 mg/kg/min). The pretreatment with enalapril alone (0.3 mg/kg plus 0.003 mg/kg/min or 1 mg/kg plus 0.01 mg/kg/min) did not alleviate the postichemic dysfunction, however, although it decreased systemic blood pressure (BP). Ischemic bed size, myocardial necrosis (by triphenyltetrazolium chloride staining), and collateral blood flow (by colored microspheres) were similar in all experimental groups. These results indicate that MCI-154 improves the postischemic contractile function of dog heart, whereas enalapril fails to improve it. ACE inhibitors may also augment the efficacy of cardiotonics on postischemic dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effects of Levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart.

A new cardiotonic agent, (R)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)-phenyl] hydrazono]propanedinitrile (Levosimendan), has been developed and screened for its ability to bind to cardiac troponin C. In perfused hearts, low concentrations of 0.03 or 0.1 mumol/L Levosimendan increased +dP/dt, but did not affect the speed of relaxation and produced only a slight increase in spontaneous heart rate in the hearts perfused with 0.1 mumol/L of the drug. In these same hearts, perfusion with 0.03 mumol/L Levosimendan did not alter the 32P incorporation into troponin I or C protein, whereas a slight but significant increase was noted for phospholamban, with no detectable change in tissue cAMP levels. Administration of 0.1 or 0.3 mumol/L Levosimendan significantly increased myocardial cAMP levels as well as the phosphorylation of phospholamban, troponin I, and C protein. Levosimendan (0.03 to 10 mumol/L) reversibly increased force generated by detergent-extracted fiber bundles over a range of submaximally activating free Ca2+ concentrations with no significant effect on maximum force or on Ca2+ binding to myofilament troponin C. There was no direct effect of Levosimendan on Ca2+ uptake by vesicles of sarcoplasmic reticulum (SR). In contrast, under conditions optimal for cAMP-dependent phosphorylation, Levosimendan slightly but significantly lowered the concentration of Ca2+, yielding half-maximal uptake rates by the SR vesicles. Our results indicate that at low concentrations Levosimendan acts preferably as a Ca2+ sensitizer, whereas at higher concentrations its action as a phosphodiesterase inhibitor contributes to the positive inotropic effect.

Analysis of Variance↗
PubMed1994

Enhancing effects of transition metals on the salt taste responses of single fibers of the frog glossopharyngeal nerve: specificity of and similarities among Ca2+, Mg2+ and Na+ taste responses.

Fibers of the frog glossopharyngeal nerve (water fibers) that are sensitive to water also respond to CaCl2, MgCl2 and NaCl. In the present study, interaction among cations (Ca2+, Mg2+ and Na+) on taste cell membrane in frogs was studied using transition metals (NiCl2, CoCl2 and MnCl2), which themselves are barely effective in producing neural response at concentrations below 5 mM. Unitary discharges from single water fibers were recorded from fungiform papillae with suction electrode. Transition metal ions (0.05-5.0 mM) had exclusively enhancing effects on the responses to 50 mM Ca2+, 100 mM Mg2+ and 500 mM Na+. The effects of transition metal ions were always reversible. The rank order of effectiveness of transition metals at 1 mM in the enhancement of the responses to 50 mM CaCl2, 100 mM MgCl2 and 500 mM NaCl was NiCl2 > CoCl2 > MnCl2. The concentration of transition metal ions effective to enhance salt response was almost the same among Ca2+, Mg2+ and Na+ responses. The results suggest that a common mechanism is involved in the enhancement of Ca2+, Mg2+ and Na+ taste responses. The enhanced Mg2+ response and the enhanced Na+ response were greatly inhibited by the addition of Ca2+ ions, and the enhanced Ca2+ response was inhibited by the addition of Mg2+ or Na+ ions, suggesting that competitive antagonism occurs between Ca2+ and Mg2+ ions and between Ca2+ and Na+ ions in the presence of Ni2+ ions. Ni2+ ions had a dual effect on the Ca2+ response induced by low concentration (0.1 mM) of CaCl2: enhancement at lower concentrations (0.02-0.1 mM) of NiCl2 and inhibition at higher concentrations (0.5-5 mM) of NiCl2. The present results suggest that transition metal ions do not affect the receptor-antagonist complex, but affect only the receptor-agonist complex.

Animals↗
PubMed1994

A quantitative study of dual action of nickel ions on the taste response to calcium ions of single fibers of the frog glossopharyngeal nerve: inhibition and enhancement by nickel ions.

Unitary discharges from single water fibers of the frog glossopharyngeal nerve, caused by stimulation with 0.02-5 mM CaSO4, were recorded from fungiform papillae with a suction electrode. NiSO4 at concentrations of 0.2-2 mM, namely, at concentrations that are barely effective in producing impulses, had a dual action on the Ca2+ response: NiSO4 caused both inhibition and enhancement of the Ca2+ response. In the present study, this dual action of Ni2+ ions on the Ca2+ response was investigated in detail. Single water fibers yielded a saturation type of concentration-response curve for CaSO4, which suggested that sulfate ions do not affect the Ca2+ response. Thus, sulfates were used as test salts in the present study. At low concentrations of Ca2+ ions, Ni2+ ions inhibited the Ca2+ response, but at higher concentrations of Ca2+ ions they enhanced it. The results can be explained quantitatively by the hypothesis that Ni2+ ions inhibit the Ca2+ response by competing with Ca2+ ions for the Ca2+ receptor (XCa) that is responsible for the Ca2+ response and that Ni2+ ions enhance the Ca2+ response by acting on a membrane element that interacts with XCa. Double-reciprocal plots of the data indicate that the enhancing action of Ni2+ ions is saturated at 1-2 mM Ni2+ ions and that Ni2+ ions at these concentrations increase the maximal response of the Ca2+ response by 182%. Dissociation constants for the Ca-XCa complex and the Ni-XCa complex were 4.2 x 10(-5) M and 7.6 x 10(-5) M, respectively. The analysis suggests that Ni2+ ions enhance the Ca2+ response by affecting the Ca-XCa complex without altering the affinity of XCa for Ca2+ ions.

Animals↗
PubMed1994

The responses to choline ions induced by transition metal ions in single water fibers of the frog glossopharyngeal nerve.

In single water-sensitive fibers (water fibers) of the frog glossopharyngeal nerve, application of a solution of 500 mM choline C1 to the tongue elicited responses of varying magnitude. Some water fibers (plain choline-insensitive water fibers) barely responded to the solution, while some water fibers (plain choline-sensitive water fibers) exhibited a considerable response to this solution. NiCl2, which is barely effective in producing neural response at concentrations below 5 mM, induced the response of plain choline-insensitive water fibers to choline+ ions. It was confirmed, in a collision test, that the Ni(2+)-induced responses to choline+ ions were derived from water fibers. However, NiCl2 did not affect the magnitude of the response generated by choline+ ions in plain choline-sensitive water fibers. The concentration-response curve for choline C1 in the presence of 1 mM NiCl2 for plain choline-insensitive water fibers was similar to the curves obtained in the absence of NiCl2 for plain choline-sensitive water fibers. Other organic salts, such as tris(hydroxymethyl)aminomethane-HCl, triethanolamine-HCl and tetraethylammonium C1, elicited no response or only a very small response from water fibers, and NiCl2 did not affect these responses. It is suggested that there exists a choline receptor for the response to choline+ ions in the apical membrane of frog taste cells and that Ni2+ ions expose the sites of such choline receptors, which are deeply embedded in the receptor membrane, to the outside medium. The effect of Ni2+ ions results in an increase in the number of the choline receptor sites available for binding of choline+ ions. The rank order of effectiveness of transition metal ions in eliciting the appearance or enhancement of the response to choline C1 was Ni2+ > Co2+ > Mn2+. Mg2+ ions had no effect on the response to choline+ ions. A similar rank order was previously obtained in enhancement of the responses to Ca2+, Mg2+ and Na+ ions (Kitada, 1994a). It seems likely that the mechanism for enhancement or elicitation of the response to choline+ ions by the transition metal ions has features in common with that for enhancement of the responses to Ca2+, Mg2+ and Na+ ions.

Animals↗
PubMed1994

Competitive inhibition of the nickel-induced response to choline by calcium ions in single water fibers of the frog glossopharyngeal nerve.

NiCl2 induces a response to choline Cl and enhances the response to CaCl2 in water-sensitive fibers (water fibers) of the frog glossopharyngeal nerve. The Ni(2+)-induced choline+ response was inhibited by Ca2+ ions and, conversely, the enhanced Ca2+ response by Ni2+ ions was inhibited by choline+ ions. Hence, there exists a mutual antagonism between Ca2+ and choline+ ions. In the present study, the inhibition of the Ni(2+)-induced choline+ response by Ca2+ ions was investigated quantitatively. The assumption was made that receptors for choline (XCh) exist and that binding of a choline+ ion to XCh brings about a neural response. It was further assumed that the magnitude of the neural response is proportional to the amount of choline-XCh complex minus some constant (the threshold concentration of the choline-XCh complex). The results from analysis of double-reciprocal plot were consistent with the hypothesis that Ca2+ ions compete with choline+ ions for XCh. The dissociation constants for the choline-XCh complex and the CaXCh complex were obtained to be 0.6 M and 7.4 x 10(-5) M, respectively. This result indicates that the affinities of XCh for choline+ and Ca2+ ions are very different. Furthermore, Mg2+ ions did not affect the Ni(2+)-induced choline+ response, an indication that the affinity of XCh is not charge-specific, but is chemically specific. The identification of a competitive inhibitor of the choline+ response provides evidence for existence of a choline-specific receptor at the surface of taste cells that are innervated by the water fibers of the frog glossopharyngeal nerve. Differences between the features of the response to choline Cl in the chorda tympani nerve of the rat and those in the frog glossopharyngeal nerve are discussed.

Animals↗
PubMed1994

EFFECTS OF DILUTED NATURAL WATER AND ALTERED IONIC ENVIRONMENTS ON GUSTATORY RESPONSES IN RAINBOW TROUT (ONCORHYNCHUS MYKISS)

1. The effects of adaptation to diluted natural water (NW) and various salt solutions on the gustatory responses recorded from the palatine nerve in rainbow trout (Oncorhynchus mykiss) were studied. 2. The magnitude of the response to 1 mmol l-1 l-proline (l-Pro) decreased when the perfusing NW was diluted with artificial fresh water (AFW) that maintained concentrations of major cations. AFW suppressed the responses to l-Pro by about 70 %. 3. The responses to 1 mmol l-1 l-Pro, 0.1 mmol l-1 quinine&shy;HCl (Q-HCl) and 10 nmol l-1 taurolithocholic acid (TLCA) were eliminated or reduced (to <10 %) by adapting the palate to distilled water (DW). The addition of 0.1&shy;100 mmol l-1 salts (NaCl, KCl, CaCl2, MgCl2) and choline chloride restored the gustatory responses to about 50 % of those in NW. The addition of salts to NW had no effect on the gustatory responses. 4. The gustatory responses to 5 % CO2 were similarly reduced when the palate was adapted to solutions that contained no NW (DW, AFW, 10 mmol l-1 NaCl in DW). However, the reduction was independent of salt concentration, suggesting a different transduction mechanism for CO2. 4. Tetrodotoxin (1 &micro;mol l-1) had no effect on the gustatory responses to l-Pro. 5. We conclude that NW is required and that cations alone are not sufficient to support maximal gustatory responses. The results suggest that an unknown substance(s) contained in NW plays an essential role in gustatory reception and that permeation of cations through the apical membrane of gustatory cells is not involved in gustatory transduction in rainbow trout.

Journal Article↗
PubMed1993

Effect of MCI-154, a cardiotonic agent, on regional contractile function and myocardial oxygen consumption in the presence and absence of coronary artery stenosis in dogs.

The effects of MCI-154 (6-[4-(4'-pyridyl)aminophenyl]-4,5-dihydro-3(2H)- pyridazinone hydrochloride.3H2O), a cardiotonic agent with calcium sensitizing actions, on regional contractile function and myocardial oxygen consumption (MVO2) were studied in the dog hearts with and without partial occlusion of the left anterior descending coronary artery and compared with those of dobutamine. Segment shortening by sonomicrometry, regional myocardial blood flow by microspheres and the oxygen content of coronary venous blood drawn from the ischemic left anterior descending coronary artery area were simultaneously measured. The ischemic zone segment shortening and left ventricular (LV) dP/dtmax were decreased after partial occlusion. The infusion of MCI-154 starting 20 min after ischemia improved the depressed segment shortening and LV dP/dtmax without increasing the ischemic zone MVO2 and regional myocardial blood flow. In the nonischemic hearts, MCI-154 did not increase MVO2 and coronary blood flow despite the augmentation of myocardial contractility. MCI-154 decreased LV end-diastolic pressure and systemic blood pressure. On the other hand, dobutamine failed to increase the ischemic zone segment shortening, but the drug increased MVO2, coronary blood flow and LV dP/dtmax in both ischemic and nonischemic hearts. These results indicate that MCI-154 alleviates the ischemic contractile failure without increasing myocardial oxygen demand. Thus, MCI-154 may be useful in the management of heart failure with reduced coronary reserve.

Animals↗
PubMed1992

Parasympathetic postganglionic nerve fibers in the fungiform papillae of the bullfrog, Rana catesbeiana.

An investigation was made of the precise origin of the unmyelinated nerve fibers in the fungiform papillae of the bullfrog's tongue. Some unmyelinated nerve fibers in the fungiform papillae originate from the parasympathetic postganglionic cells in the glossopharyngeal nerve. Axonal enlargements of the parasympathetic nerve fibers were in close contact with the Merkel-like basal or supporting cells in the taste disk. These results seem to provide morphological evidence for the existence of an efferent control system in the taste disk.

Animals↗
PubMed1992

Beneficial effect of MCI-154, a cardiotonic agent, on ischemic contractile failure and myocardial acidosis of dog hearts: comparison with dobutamine, milrinone and pimobendan.

The effects of MCI-154, a cardiotonic agent with Ca++ sensitizing actions, on the ischemic contractile failure and myocardial acidosis were studied in the dog heart, in which the left anterior descending coronary artery (LAD) was partially occluded for 90 min, and compared with those of dobutamine, milrinone, pimobendan and isosorbide dinitrate (ISDN). Partial occlusion of LAD decreased segment shortening (measured by sonomicrometry) and myocardial pH (assessed by a micro glass pH electrode) in the ischemic myocardium. MCI-154, when administered i.v. 30 min after ischemia, improved the segment shortening in the ischemic zone, whereas dobutamine, milrinone and pimobendan failed to improve it when the drugs increased peak positive left ventricular dP/dt. Among the cardiotonic agents tested only MCI-154 attenuated myocardial acidosis during ischemia. The degree of the attenuation of acidosis by MCI-154 was equivalent with that by ISDN. However, the improvement of the ischemic zone segment shortening by MCI-154 was more pronounced than that by ISDN. These results suggest that in addition to the attenuation of myocardial acidosis the positive inotropic action of MCI-154, presumably increasing the responses of myofilaments to Ca++, may be possibly responsible for the improvement of regional contractile function in the ischemic myocardium. Thus, MCI-154 may be useful in the management of ischemic heart failure.

Acidosis↗
PubMed1991

Improvement of postischemic contractile dysfunction of dog heart by MCI-154, a novel cardiotonic agent.

The effects of MCI-154, a cardiotonic agent which has direct effects on cardiac myofilaments, on postischemic contractile dysfunction were studied in dog heart subjected to a 30-min occlusion of the left anterior descending coronary artery followed by reperfusion, and compared with the effects of milrinone and dobutamine, that have largely cyclic AMP-dependent mechanisms of action. Regional myocardial contractility (segment shortening) and tissue ATP levels were severely depressed in reperfused myocardium. MCI-154 (0.3 and 1 microgram/kg per min) improved the regional function of postischemic myocardium and decreased left ventricular end-diastolic pressure and systemic aortic pressure when infused i.v. from 30 min after reperfusion. The improvement of regional function caused by MCI-154 (1 microgram/kg per min) was more pronounced than that caused by milrinone (1 microgram/kg per min) or dobutamine (1 microgram/kg per min), although the drugs produced an equal increase in cardiac performance (peak positive left ventricular dP/dt). These results suggest that MCI-154 produces a more pronounced improvement of regional myocardial function than milrinone and dobutamine, presumably by increasing the responses of the contractile protein system to Ca2+. In this respect, MCI-154 would be of much benefit for the treatment of postischemic left ventricular dysfunction.

Adenosine Triphosphate↗
PubMed1991

Parasympathetic postganglionic cells in the glossopharyngeal nerve trunk and their relationship to unmyelinated nerve fibers in the fungiform papillae of the frog.

The glossopharyngeal nerve of the frog is made up of afferent nerve fibers and efferent, parasympathetic and sympathetic nerve fibers. The precise origin and course of the parasympathetic efferent nerve fibers in the fungiform papillae of the frog's tongue were investigated. We found the ganglionic cells in the lingual branch of the frog glossopharyngeal nerve. The surface of the ganglionic cell bodies was partly covered by synaptic endings that impinged upon it. Synaptic endings contained clear synaptic vesicles and large dense-cored vesicles. After cutting of the glossopharyngeal nerve proximal to the jugular ganglion, synaptic endings were found to show definite signs of degeneration. These findings led us to the conclusion that the ganglionic cells in the lingual branch of the glossopharyngeal nerve are the parasympathetic postganglionic cells. After cutting of the glossopharyngeal nerve distal to the jugular ganglion, some unmyelinated nerve fibers in the fungiform papillae and postganglionic cells in the lingual branch remained intact. These results strongly suggest that the origin of some of the unmyelinated nerve fibers is the parasympathetic postganglionic cell in the lingual branch.

Animals↗
PubMed1991

MCI-154, a novel cardiotonic agent, reverses the acidic pH-induced decrease in responses of cardiac myofilaments to Ca++: comparison with sulmazole and pimobendan.

In the present study, we have examined the effects of decreasing pH from 7.0 to 6.6 on the tension developed by direct activation of the myofilaments in chemically skinned fibers from guinea pig papillary muscles. We then compared the effects of the novel inotropic agents MCI-154, pimobendan and sulmazole, which have direct action on cardiac myofilaments, on the acidic pH-induced changes in responses of the contractile system to Ca++. The reduction of pH from 7.0 to 6.8 shifted the pCa (-log[Ca++] M)-tension relation curve to the right with no change in maximum tension. However, the reduction of pH from 7.0 to 6.6 shifted the pCa tension relation curve to the right and also depressed maximum force development. These effects were reversible by returning to neutral pH (pH 7.0), but were not overcome by increasing the free [Ca++] (decreasing pCa from 4.4 to 4.0). The amplitude of pMg-ATP (-log[MgATP]M)-tension curve in the absence of free Ca++ (Ca++ less than 1 nM, bell-shaped curve) was shifted downward by reducing pH from 7.0 to 6.6. MCI-154 (1-100 microM) reversed the acidic pH-induced decrease of tension development which was activated by pCa 5.8 in a concentration-dependent manner. Moreover, the acidosis induced reductions of maximum tension (pCa, 4.4) and pMgATP 6.0-activated tension (Ca++ less than 1 nM) were also reversed by MCI-154 (1-100 microM) in a concentration-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1990

Taste responses to electrolytes in the frog glossopharyngeal nerve: initial process of taste reception.

In taste reception, it has been proposed that changes in surface potential on the apical membrane of taste cells bring about activation of taste cells during chemical stimulation. To ascertain whether changes in the surface potential are involved in taste reception of electrolytes, unitary discharges were recorded from single water fibers of the frog glossopharyngeal nerve with a suction electrode. The surface potential is a function of both the charge density of the membrane surface and the ionic strength of the medium. Low concentrations of CaCl2 (less than 1 mM) were very effective stimuli. However, 0.01-1 mM LaCl3 and HCl (pH 3.0-4.5), which alter the surface potential in the positive direction, had no excitatory effect. Transition metal cations, such as Mn2+, Co2 and Ni2+, had an excitatory effect, but the responses to these cations appeared at relatively high concentrations (greater than 5 mM), in spite of the high affinity of the receptor membrane for these cations. The results suggest that the surface charge of the apical membrane is not associated with the excitation caused by electrolytes. MgCl2 (greater than 5 mM) and NaCl (greater than 100 mM) were also effective stimuli, whereas choline Cl (100-1000 mM) had no excitatory effect. An increase in the ionic strength was achieved by the addition of 100-300 mM choline Cl to stimulating solutions of MgCl2 or NaCl. The responses to Mg2+ and Na+ were not affected by the increase in the ionic strength. The results obtained here indicate that changes in the surface potential on the surface of the apical membrane are not involved in taste reception of electrolytes. Alteration of the surface potential of the membrane in the positive direction would bring about a reduction in the local concentration of cations in the vicinity of the membrane. Hence, the presence of divalent cations in the medium may affect the response to monovalent cations. However, addition of 100 mM MgCl2 to the stimulating solution of NaCl did not affect the concentration-response curve for NaCl. This result suggests that the surface charge density of the apical membrane is very low and hence the magnitude of the surface potential is very small. The results also suggest that Mg2+ and Na+ activate the taste cells by two separate, non-interacting processes. The present study suggests that, in the initial process of taste reception, only the binding of each separate cation to its appropriate receptor site (specific receptor site) leads to activation of the receptor.

Animals↗
PubMed1990

Effects of MCI-154, a novel cardiotonic agent, on mean circulatory filling pressure in anesthetized dogs.

The effects of MCI-154, a novel cardiotonic agent, on mean circulatory filling pressure (an index of total body venous tone), total peripheral resistance and the heart were examined in anesthetized dogs. The bolus injection of MCI-154 (10-100 micrograms/kg i.v.) caused a dose-dependent decrease in mean circulatory filling pressure and resistance to venous return. MCI-154 also decreased the mean blood pressure and total peripheral resistance, and increased cardiac output and heart rate. Right atrial pressure was reduced only by the lowest dose (10 micrograms/kg i.v.) of MCI-154. These hemodynamic effects of MCI-154, except those on mean circulatory pressure and resistance to venous return, reached a maximum with 30 micrograms/kg of the drug. Nitroglycerin (50 micrograms/kg i.v.), a venodilator, decreased mean circulatory filling pressure, resistance to venous return, mean blood pressure and total peripheral resistance, and increased heart rate. However, unlike MCI-154, nitroglycerin did not alter cardiac output and right atrial pressure. These results suggest that the venodilator effect of MCI-154, as well as the positive inotropic and vasodilator effects, could potentially benefit patients with congestive heart failure.

Anesthesia↗
PubMed1990

[Antihypertensive effect of betaxolol, a cardioselective beta-adrenoceptor antagonist, in renal hypertensive dogs].

The antihypertensive effect of betaxolol, a highly selective beta 1-adrenoceptor antagonist, was investigated in renal hypertensive dogs, and the mechanism was also studied. A single oral administration of betaxolol (1 and 10 mg/kg) lowered blood pressure dose-dependently. The hypotensive effect of betaxolol was enhanced by daily oral administration for 10 days. In anesthetized dogs, intraarterial injection of betaxolol produced a dose-dependent increase in femoral artery flow; and in this test, betaxolol was 3 times less potent than papaverine. The increase in blood flow with betaxolol was not affected by pretreatment with propranolol. These findings indicate that a certain vasodilating activity may contribute to the antihypertensive mechanism of betaxolol.

Adrenergic beta-Antagonists↗