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  • 1
    ISSN: 1432-1912
    Keywords: α-and β-Adrenoceptors ; Methoxamine ; Isoprenaline ; cAMP ; Papaverine ; Rabbit Papillary Muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the isolated papillary muscle of the rabbit the time course of the effects of selective β-and α-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3′,5′-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3×10−7 M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10−4 M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10−5 M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile force and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3×10−7 M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10−4 M) was not affected by papaverine (10−5 M). Further-more, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by β-adrenoceptor stimulation, and indicate further that the stimulation of α-adrenoceptors evokes its positive inotropic effect through a mechanism other than that elicited by β-adrenoceptor stimulation, i.e., independent of cAMP.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 284 (1974), S. 133-148 
    ISSN: 1432-1912
    Keywords: Adrenoceptors ; Phenylephrine ; Phosphodiesterase Inhibitors ; Rabbit Papillary Muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On the isolated papillary muscle of the rabbit experiments were performed in order to study whether β-and/or α-adrenoceptors mediate the positive inotropic effect of phenylephrine and, for comparison, of other sympathomimetic drugs. 1. The positive inotropic effect of phenylephrine in concentrations of up to 3×10−6M was antagonized by the α-adrenolytic drug phentolamine, while that evoked by higher concentrations was inhibited by the β-adrenolytic drug pindolol. The intrinsic activity of phenylephrine amounted to 0.6 compared with that of isoprenaline. 2. Pretreatment with reserpine altered neither the pD2-value for phenylephrine nor its intrinsic activity. 3. The inhibitors of phosphodiesterase, theophylline (10−4M) and papaverine (10−5M) enhanced the effect of higher concentrations of phenylephrine—mediated mainly by stimulation of β-adrenoceptors, whereas that of lower concentrations—mediated by stimulation of α-adrenoceptors—was not affected. Papaverine strongly increased the intrinsic activity of phenylephrine, which then reached that of isoprenaline. 4. The α-adrenoceptor stimulating drugs, methoxamine, naphazoline and oxymetazoline did not cause positive inotropic effects but, on the contrary, negative ones. The positivei notropic effect of noradrenaline was not changed by phentolamine, whereas that of adrenaline in concentrations of up to 10−5 M was inhibited. 5. From these results it is concluded that in the rabbit papillary muscle not only β- but also α-adrenoceptors are of functional importance for the mediation of the positive inotropic effect of some sympathomimetic drugs. The nature of these α-adrenoceptors is apparently distinct from those of other organs since these receptors were stimulated only by phenylephrine and adrenaline but not by noradrenaline, methoxamine, naphazoline and oxymetazoline.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 61-72 
    ISSN: 1432-1912
    Keywords: α-Adrenoceptors ; Frequency-Force Relationship ; Temperature ; D600 ; Rabbit Papillary Muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On the isolated rabbit papillary muscle experiments were carried out to determine whether the positive inotropic effects mediated by α- and by β-adrenoceptors are brought about by different mechanisms or not.—For this reason the influence of temperature and the effect of the calcium antagonist D600 on the responses to phenylephrine and to isoprenaline were compared. 1. The maximal inotropic effects of phenylephrine, isoprenaline and calcium were not affected by raising the temperature of the organ bath from 37° to 42°C whereas the basal developed tension of the muscle was significantly decreased. 2. The dose-response curve for phenylephrine was markedly shifted to the right by raising the temperature (ΔpD 2=0.89), while that for isoprenaline was also shifted to the right, but to a lesser extent (ΔpD 2=0.23). 3. In the presence of 1.5 × 10−8M pindolol the shift of the dose-response curve for phenylephrine induced by elevation of temperature was more prominent (ΔpD 2=1.91), whereas phentolamine (3 × 10−6M) inhibited the temperatureinduced shift. 4. The positive inotropic effect of phenylephrine—mediated by α-adrenoceptors under blockade of β-adrenoceptors by 1.5 × 10−8M pindolol—was markedly depressed by D600 (10−7 and 3 × 10−7M): the dose-response curve was shifted to the right and the maximal response was depressed. On the other hand, the positive inotropic effect of isoprenaline—mediated by β-adrenoceptors—was affected to a lesser extent by D600 and the maximal response was not changed. 5. These results indicate that the stimulation of α-adrenoceptors in the rabbit papillary muscle induces a positive inotropic response through a biochemical process different from that caused via β-adrenoceptors, i.e., stimulation of α-adrenoceptors may increase the intracellular calcium level mainly by changing the transmembrane calcium flux.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 287 (1975), S. 377-389 
    ISSN: 1432-1912
    Keywords: α-Adrenoceptors ; Methoxamine ; Naphazoline ; Frequency-force Relationship ; Rabbit Papillary Muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Under the conditions of different stimulation frequencies the inotropic effects of the α-adrenoceptor stimulating agents, methoxamine, naphazoline and oxymetazoline were studied on the isolated rabbit papillary muscle. 1. On the papillary muscle stimulated at 0.5 Hz methoxamine in concentrations from 10−5 to 3×10−4 M caused a significant and dose-dependent positive inotropic effect. At 10−3 M methoxamine decreased the developed tension. With increasing frequency of stimulation (0.5–1–1.5 Hz), the positive inotropic effect became smaller, while the negative inotropic one was more pronounced. The time course of the disappearance of the negative inotropic effect of methoxamine by washout differed from that of the positive inotropic effect: the negative component disappeared within 30 min, whereas the positive one lasted for about 100 min. The positive inotropic effect of noradrenaline (10−6 M), in contrast to that of methoxamine, was not influenced by the frequency under the same conditions of stimulation. Also naphazoline (10−5 M) caused a significant positive inotropic effect on the papillary muscle stimulated at 0.5 Hz, while oxymetazoline induced exclusively a negative inotropic effect. 2. The positive inotropic effect of methoxamine (10−4 M) as well as of naphazoline (10−5 M) evoked at a frequency of 0.5 Hz was abolished by phentolamine (10−6 M). Methoxamine (10−4 M) induced a significant negative inotropic effect in the presence of phentolamine. Phentolamine antagonized the positive inotropic effect of methoxamine in a non-competitive manner: the pD′2-value was 7.76. 3. In the presence of methoxamine (10−4 M) the developed tension in the lower range (0.05–1 Hz) of the frequency-force relationship was enhanced, while that in the higher range (〉1.5 Hz) was decreased. The enhancement was abolished by phentolamine (10−6 M). 4. Papaverine (2×10−5 M) did not affect the positive inotropic effect of methoxamine. 5. The present results show that methoxamine and naphazoline induced a positive inotropic effect via α-adrenoceptors in the ventricular myocardium of the rabbit. These effects were caused only at low, but not at high frequencies of stimulation.
    Type of Medium: Electronic Resource
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