The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform
Allan D. Struthers - One of the best experts on this subject based on the ideXlab platform.
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Angiotensin II augments the stroke volume response to Isoprenaline in man.
Journal of hypertension, 1991Co-Authors: Ph Seidelin, Allan D. StruthersAbstract:Many studies in experimental animal models suggest that there is an interaction between angiotensin II and the sympathetic nervous system. We have now sought evidence for such an interaction using angiotensin II and beta-adrenoceptor stimulation with Isoprenaline. Ten normal volunteers were infused with placebo/placebo, placebo/angiotensin II, placebo/Isoprenaline and angiotensin II/Isoprenaline in a randomized single-blind fashion. Isoprenaline alone caused a non-significant 11-20% rise in stroke volume. Angiotensin II alone caused no significant change in stroke volume. However, the combination of angiotensin II/Isoprenaline caused a significant increase in stroke volume of 31-55% (p less than 0.01), and this increase was significantly greater than with Isoprenaline alone (P less than 0.02, by repeated-measures analysis of variance). This occurred with no difference in heart rate change. Isoprenaline significantly reduced total peripheral resistance and this reduction was not affected by concomitant infusion of angiotensin II. This study provides evidence that a physiological dose of angiotensin II can synergistically augment the stroke volume effect of beta-agonism in man. There are several possible mechanisms, but a regional redistribution of venous blood which causes increased cardiac filling seems likely.
Ph Seidelin - One of the best experts on this subject based on the ideXlab platform.
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Angiotensin II augments the stroke volume response to Isoprenaline in man.
Journal of hypertension, 1991Co-Authors: Ph Seidelin, Allan D. StruthersAbstract:Many studies in experimental animal models suggest that there is an interaction between angiotensin II and the sympathetic nervous system. We have now sought evidence for such an interaction using angiotensin II and beta-adrenoceptor stimulation with Isoprenaline. Ten normal volunteers were infused with placebo/placebo, placebo/angiotensin II, placebo/Isoprenaline and angiotensin II/Isoprenaline in a randomized single-blind fashion. Isoprenaline alone caused a non-significant 11-20% rise in stroke volume. Angiotensin II alone caused no significant change in stroke volume. However, the combination of angiotensin II/Isoprenaline caused a significant increase in stroke volume of 31-55% (p less than 0.01), and this increase was significantly greater than with Isoprenaline alone (P less than 0.02, by repeated-measures analysis of variance). This occurred with no difference in heart rate change. Isoprenaline significantly reduced total peripheral resistance and this reduction was not affected by concomitant infusion of angiotensin II. This study provides evidence that a physiological dose of angiotensin II can synergistically augment the stroke volume effect of beta-agonism in man. There are several possible mechanisms, but a regional redistribution of venous blood which causes increased cardiac filling seems likely.
Martin C. Michel - One of the best experts on this subject based on the ideXlab platform.
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Agonist-induced desensitization of human β_3-adrenoceptors expressed in human embryonic kidney cells
Naunyn-Schmiedeberg's Archives of Pharmacology, 2013Co-Authors: Martina B. Michel-reher, Martin C. MichelAbstract:β_3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β_3-adrenoceptor desensitization in HEK cells. Cells were treated with Isoprenaline or forskolin, and following wash-out, cyclic adenosine monophosphate (cAMP) accumulation in response to freshly added agonist was quantified. Receptor and G protein expression were quantified by radioligand binding and immunoblot experiments, respectively. Treatment with Isoprenaline induced a concentration- and time-dependent desensitization of cAMP accumulation in response to freshly added Isoprenaline. This functional desensitization primarily consisted of reduced maximum responses with little change of agonist potency. Maximum desensitization was achieved by pre-treatment with 10 μM Isoprenaline for 24 h. It was not accompanied by changes in β_3-adrenoceptor density as assessed in saturation radioligand-binding studies. The desensitization was associated with a small reduction in immunoreactivity for α-subunits for G_s and G_i1, whereas that for G_i2, G_i3, and G_q/11 was not significantly altered. In cells treated with pertussis toxin, Isoprenaline-induced cAMP accumulation as well as desensitization by Isoprenaline pre-treatment remained unchanged. Isoprenaline pre-treatment also reduced forskolin-induced cAMP accumulation; conversely, pre-treatment with forskolin caused a similar desensitization of Isoprenaline-induced cAMP accumulation. We conclude that agonist-induced β_3-adrenoceptor desensitization in HEK cells does not involve reduced receptor numbers and small, if any, reduction of G_s expression; changes at the level of adenylyl cyclase function can fully explain this desensitization.
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Agonist-induced desensitization of human β_3-adrenoceptors expressed in human embryonic kidney cells
Naunyn-Schmiedeberg's Archives of Pharmacology, 2013Co-Authors: Martina B. Michel-reher, Martin C. MichelAbstract:β_3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β_3-adrenoceptor desensitization in HEK cells. Cells were treated with Isoprenaline or forskolin, and following wash-out, cyclic adenosine monophosphate (cAMP) accumulation in response to freshly added agonist was quantified. Receptor and G protein expression were quantified by radioligand binding and immunoblot experiments, respectively. Treatment with Isoprenaline induced a concentration- and time-dependent desensitization of cAMP accumulation in response to freshly added Isoprenaline. This functional desensitization primarily consisted of reduced maximum responses with little change of agonist potency. Maximum desensitization was achieved by pre-treatment with 10 μM Isoprenaline for 24 h. It was not accompanied by changes in β_3-adrenoceptor density as assessed in saturation radioligand-binding studies. The desensitization was associated with a small reduction in immunoreactivity for α-subunits for G_s and G_i1, whereas that for G_i2, G_i3, and G_q/11 was not significantly altered. In cells treated with pertussis toxin, Isoprenaline-induced cAMP accumulation as well as desensitization by Isoprenaline pre-treatment remained unchanged. Isoprenaline pre-treatment also reduced forskolin-induced cAMP accumulation; conversely, pre-treatment with forskolin caused a similar desensitization of Isoprenaline-induced cAMP accumulation. We conclude that agonist-induced β_3-adrenoceptor desensitization in HEK cells does not involve reduced receptor numbers and small, if any, reduction of G_s expression; changes at the level of adenylyl cyclase function can fully explain this desensitization.
Richard J. Haslam - One of the best experts on this subject based on the ideXlab platform.
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Synergistic actions of nitrovasodilators and Isoprenaline on rat aortic smooth muscle.
European journal of pharmacology, 1991Co-Authors: Donald H. Maurice, Denis J. Crankshaw, Richard J. HaslamAbstract:Previous studies have established that nitrovasodilators potentiate the inhibition of platelet function by activators of adenylyl cyclase, but uncertainty exists as to whether a comparable effect is seen in vascular smooth muscle. We initially studied the effects of the nitrovasodilators, sodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), on the relaxation by Isoprenaline of rat aortic smooth muscle that had been precontracted by phenylephrine. Concentrations of SNP (0.25 nM) and SIN-1 (30 nM) that relaxed aortic smooth muscle less than 30% alone, caused significant (3-fold) decreases in the IC50 values for Isoprenaline. The cAMP phosphodiesterase inhibitors, cilostamide (20 nM) and Ro 20-1724 (10 microM), caused comparable reductions in the IC50 values for Isoprenaline. At these concentrations, each of the four compounds also increased the maximum relaxation achieved with Isoprenaline. Even more marked synergistic interactions were observed between Isoprenaline and either the nitrovasodilators or the cAMP phosphodiesterase inhibitors when these compounds were added simultaneously before contraction of aortic smooth muscle by phenylephrine. Thus, concentrations of SNP (5 nM), SIN-1 (1 microM), cilostamide (1 microM) and Ro 20-1724 (100 microM) that inhibited contraction by less than 30% decreased the IC50 values for Isoprenaline by 8- to 10-fold. At the above concentrations, these compounds each caused a supra-additive inhibition of contraction when added with 100 nM Isoprenaline. Thus, synergism between nitrovasodilators and Isoprenaline, an activator of adenylyl cyclase, could be detected in vascular smooth muscle and was particularly marked when inhibition of contraction was studied. This action of nitrovasodilators resembled that of inhibitors of cAMP phosphodiesterase.
Martina B. Michel-reher - One of the best experts on this subject based on the ideXlab platform.
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Agonist-induced desensitization of human β_3-adrenoceptors expressed in human embryonic kidney cells
Naunyn-Schmiedeberg's Archives of Pharmacology, 2013Co-Authors: Martina B. Michel-reher, Martin C. MichelAbstract:β_3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β_3-adrenoceptor desensitization in HEK cells. Cells were treated with Isoprenaline or forskolin, and following wash-out, cyclic adenosine monophosphate (cAMP) accumulation in response to freshly added agonist was quantified. Receptor and G protein expression were quantified by radioligand binding and immunoblot experiments, respectively. Treatment with Isoprenaline induced a concentration- and time-dependent desensitization of cAMP accumulation in response to freshly added Isoprenaline. This functional desensitization primarily consisted of reduced maximum responses with little change of agonist potency. Maximum desensitization was achieved by pre-treatment with 10 μM Isoprenaline for 24 h. It was not accompanied by changes in β_3-adrenoceptor density as assessed in saturation radioligand-binding studies. The desensitization was associated with a small reduction in immunoreactivity for α-subunits for G_s and G_i1, whereas that for G_i2, G_i3, and G_q/11 was not significantly altered. In cells treated with pertussis toxin, Isoprenaline-induced cAMP accumulation as well as desensitization by Isoprenaline pre-treatment remained unchanged. Isoprenaline pre-treatment also reduced forskolin-induced cAMP accumulation; conversely, pre-treatment with forskolin caused a similar desensitization of Isoprenaline-induced cAMP accumulation. We conclude that agonist-induced β_3-adrenoceptor desensitization in HEK cells does not involve reduced receptor numbers and small, if any, reduction of G_s expression; changes at the level of adenylyl cyclase function can fully explain this desensitization.
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Agonist-induced desensitization of human β_3-adrenoceptors expressed in human embryonic kidney cells
Naunyn-Schmiedeberg's Archives of Pharmacology, 2013Co-Authors: Martina B. Michel-reher, Martin C. MichelAbstract:β_3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β_3-adrenoceptor desensitization in HEK cells. Cells were treated with Isoprenaline or forskolin, and following wash-out, cyclic adenosine monophosphate (cAMP) accumulation in response to freshly added agonist was quantified. Receptor and G protein expression were quantified by radioligand binding and immunoblot experiments, respectively. Treatment with Isoprenaline induced a concentration- and time-dependent desensitization of cAMP accumulation in response to freshly added Isoprenaline. This functional desensitization primarily consisted of reduced maximum responses with little change of agonist potency. Maximum desensitization was achieved by pre-treatment with 10 μM Isoprenaline for 24 h. It was not accompanied by changes in β_3-adrenoceptor density as assessed in saturation radioligand-binding studies. The desensitization was associated with a small reduction in immunoreactivity for α-subunits for G_s and G_i1, whereas that for G_i2, G_i3, and G_q/11 was not significantly altered. In cells treated with pertussis toxin, Isoprenaline-induced cAMP accumulation as well as desensitization by Isoprenaline pre-treatment remained unchanged. Isoprenaline pre-treatment also reduced forskolin-induced cAMP accumulation; conversely, pre-treatment with forskolin caused a similar desensitization of Isoprenaline-induced cAMP accumulation. We conclude that agonist-induced β_3-adrenoceptor desensitization in HEK cells does not involve reduced receptor numbers and small, if any, reduction of G_s expression; changes at the level of adenylyl cyclase function can fully explain this desensitization.
