E-Swift25
New member
Keeping your beta-2 receptors fresh has been somewhat of a nuisance for those of us that use Invalid Link Removed or albuterol, specifically. Ketotifen has been shown to help sensitize your receptors, but can be counter productive to a certain extent. Antihistamines can actually cause weight gain. The concomitant use of ketotifen and Invalid Link Removed will decrease the effectiveness of the Invalid Link Removed, but in turn, will stave off tolerance and increase the legnth of prodcutive use. Hopefully, we can find new, innovative ways to circumvent this problem. Dexamethasone is a corticosteroid, meaning that it is catabolic to muscle tissue. I highly doubt that a few days on Dexamethasone is going to exhibit any negligible effect on muscle tissue. If someone used it with anabolics, the negative effects would be next to none.
Possible Role of Dexamethasone in Sensitizing the Beta-2-Adrenergic Receptor System in vivo in Calves during Concomitant Treatment with Invalid Link Removed G. Abrahama, J. Gottschalkb, F. R. Ungemacha
aInstitute of Pharmacology, Pharmacy and Toxicology, and
bDepartment of Physiological Chemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
Address of Corresponding Author
Pharmacology 2004;72:196-204 (DOI: 10.1159/000080105)
goto top of page Key Words
* Mononuclear leukocytes
* Drug activation
* beta-Adrenoceptor regulation
* Adenosine 3',5'-cyclic monophosphate
goto top of page Abstract
beta2-Agonists blunt the function of the beta-adrenoceptor G-protein adenylate cyclase-signalling system, whereas glucocorticoids reverse the agonist-mediated diminished beta-adrenergic responses; however, these effects have not been reported in vivo in calf lymphocytes. In this study, we first investigated the presence of the beta2-adrenergic receptors on calf lymphocytes, and second we tested the effects of either Invalid Link Removed alone or in combination with dexamethasone on receptor expression and function (isoproterenol-induced intracellular adenosine 3',5'-cyclic monophosphate (cAMP) formation) in vivo. (-)-[125I]-Iodocyanopindolol (ICYP) binding to intact calf lymphocytes was rapid, saturable (maximal number of binding sites 987 ± 89 ICYP-binding sites/cell, n = 4) and of high affinity (KD value 17.23 ± 2.8 pmol/l, n = 4). These binding sites were of the beta2-subtypes of adrenoceptors as indicated by the fact that beta-agonists inhibited ICYP binding with an order of potency: (-)-isoproterenol > (-)-adrenaline > (-)-noradrenaline. Furthermore, the selective beta2-adrenoceptor antagonist ICI 118.551 was about >1,500 times more potent in inhibiting ICYP binding than was the beta1-selective adrenoceptor antagonist CGP 20712A. Consequently, calves were treated with Invalid Link Removed (1.0 µg/kg b.i.d., i.v.) for 9 days alone or simultaneously with dexamethasone (0.1 mg/kg, i.v., once a day for 4 days). Invalid Link Removed decreased the number of lymphocyte beta2-adrenergic receptors by about 40-50% after only 48 h of drug administration. This was accompanied by a decrement in isoproterenol-induced lymphocyte cAMP formation. Upon application of both drugs, dexamethasone restored the clenbuterol-mediated decrease in beta2-adrenoceptors and cAMP production. Dexamethasone elevated the number of beta2-adrenoceptors and cAMP almost 1.5- to 2-fold at 24 h of drug administration, an effect that persisted for up to 24 h following drug withdrawal. Neither Invalid Link Removed nor the combination with dexamethasone had an influence on the affinity of the receptor for the ligand. The present results demonstrate that dexamethasone in vivo upregulates the number and function of calf lymphocyte beta2-adrenoceptors, and thus enhances the sensitivity of the beta2-adrenoceptor signal-transduction pathway for Invalid Link Removed during concomitant treatment with both drugs.
Effects of beta 2-agonist- and dexamethasone-treatment on relaxation and regulation of beta-adrenoceptors in human bronchi and lung tissue.
Hauck RW, Harth M, Schulz C, Prauer H, Bohm M, Schomig A.
1. Medizinischen Klinik und Poliklinik, Technische Universitat, Munchen, Germany.
1. Long-term treatment with beta 2-adrenoceptor agonists can lead to a decreased therapeutic efficacy of bronchodilatation in patients with obstructive pulmonary disease. In order to examine whether or not this is due to beta-adrenoceptor desensitization, human bronchial muscle relaxation was studied in isolated bronchial rings after pretreatment with beta 2-adrenoceptor agonists. Additionally, the influence of pretreatment with dexamethasone on desensitization was studied. 2. The effect of beta 2-agonist incubation alone and after coincubation with dexamethasone on density and affinity of beta-adrenoceptors was investigated by radioligand binding experiments. 3. In human isolated bronchi, isoprenaline induces a time- and concentration-dependent beta-adrenoceptor desensitization as judged from maximal reduction in potency by a factor of 7 and reduction of 73 +/- 4% in efficacy of isoprenaline to relax human bronchial smooth muscle. 4. After an incubation period of 60 min with 100 mumol l-1 terbutaline, a significant decline in its relaxing efficacy (81 +/- 8%) and potency (by a factor 5.5) occurred. 5. Incubation with 30 mumol l-1 isoprenaline for 60 min did not impair the maximal effect of a subsequent aminophylline response but led to an increase in potency (factor 4.4). 6. Coincubation of dexamethasone with isoprenaline (120 min; 30 mumol l-1) preserved the effect of isoprenaline on relaxation (129 +/- 15%). 7. In radioligand binding experiments, pretreatment of lung tissue for 60 min with isoprenaline (30 mumol l-1) resulted in a decrease in beta-adrenoceptor binding sites (Bmax) to 64 +/- 1.6% (P < 0.05), while the antagonist affinity (KD) for [3H]-CGP-12177 remained unchanged. 8. In contrast, radioligand binding studies on lung tissue pretreated with either dexamethasone (30 mumol l-1) or isoprenaline (30 mumol l-1) plus dexamethasone (30 mumol l-1) for 120 min did not lead to a significant change of Bmax (160 +/- 22.1% vs 142.3 +/- 28.7%) or KD (5.0 nmol l-1 vs 3.5 nmol l-1) compared to the controls. 9. In conclusion, pretreatment of human bronchi with beta-adrenoceptor agonists leads to functional desensitization and, in lung tissue, to down-regulation of beta-adrenoceptors. This effect can be counteracted by additional administration of dexamethasone. Our model of desensitization has proved useful for the identification of mechanisms of beta-adrenoceptor desensitization and could be relevant for the evaluation of therapeutic strategies to counteract undesirable effects of long-term beta-adrenoceptor stimulation.
Interesting read, but hypothetical at this point. If anyone has used it or has any other input, please contribute.
Possible Role of Dexamethasone in Sensitizing the Beta-2-Adrenergic Receptor System in vivo in Calves during Concomitant Treatment with Invalid Link Removed G. Abrahama, J. Gottschalkb, F. R. Ungemacha
aInstitute of Pharmacology, Pharmacy and Toxicology, and
bDepartment of Physiological Chemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
Address of Corresponding Author
Pharmacology 2004;72:196-204 (DOI: 10.1159/000080105)
goto top of page Key Words
* Mononuclear leukocytes
* Drug activation
* beta-Adrenoceptor regulation
* Adenosine 3',5'-cyclic monophosphate
goto top of page Abstract
beta2-Agonists blunt the function of the beta-adrenoceptor G-protein adenylate cyclase-signalling system, whereas glucocorticoids reverse the agonist-mediated diminished beta-adrenergic responses; however, these effects have not been reported in vivo in calf lymphocytes. In this study, we first investigated the presence of the beta2-adrenergic receptors on calf lymphocytes, and second we tested the effects of either Invalid Link Removed alone or in combination with dexamethasone on receptor expression and function (isoproterenol-induced intracellular adenosine 3',5'-cyclic monophosphate (cAMP) formation) in vivo. (-)-[125I]-Iodocyanopindolol (ICYP) binding to intact calf lymphocytes was rapid, saturable (maximal number of binding sites 987 ± 89 ICYP-binding sites/cell, n = 4) and of high affinity (KD value 17.23 ± 2.8 pmol/l, n = 4). These binding sites were of the beta2-subtypes of adrenoceptors as indicated by the fact that beta-agonists inhibited ICYP binding with an order of potency: (-)-isoproterenol > (-)-adrenaline > (-)-noradrenaline. Furthermore, the selective beta2-adrenoceptor antagonist ICI 118.551 was about >1,500 times more potent in inhibiting ICYP binding than was the beta1-selective adrenoceptor antagonist CGP 20712A. Consequently, calves were treated with Invalid Link Removed (1.0 µg/kg b.i.d., i.v.) for 9 days alone or simultaneously with dexamethasone (0.1 mg/kg, i.v., once a day for 4 days). Invalid Link Removed decreased the number of lymphocyte beta2-adrenergic receptors by about 40-50% after only 48 h of drug administration. This was accompanied by a decrement in isoproterenol-induced lymphocyte cAMP formation. Upon application of both drugs, dexamethasone restored the clenbuterol-mediated decrease in beta2-adrenoceptors and cAMP production. Dexamethasone elevated the number of beta2-adrenoceptors and cAMP almost 1.5- to 2-fold at 24 h of drug administration, an effect that persisted for up to 24 h following drug withdrawal. Neither Invalid Link Removed nor the combination with dexamethasone had an influence on the affinity of the receptor for the ligand. The present results demonstrate that dexamethasone in vivo upregulates the number and function of calf lymphocyte beta2-adrenoceptors, and thus enhances the sensitivity of the beta2-adrenoceptor signal-transduction pathway for Invalid Link Removed during concomitant treatment with both drugs.
Effects of beta 2-agonist- and dexamethasone-treatment on relaxation and regulation of beta-adrenoceptors in human bronchi and lung tissue.
Hauck RW, Harth M, Schulz C, Prauer H, Bohm M, Schomig A.
1. Medizinischen Klinik und Poliklinik, Technische Universitat, Munchen, Germany.
1. Long-term treatment with beta 2-adrenoceptor agonists can lead to a decreased therapeutic efficacy of bronchodilatation in patients with obstructive pulmonary disease. In order to examine whether or not this is due to beta-adrenoceptor desensitization, human bronchial muscle relaxation was studied in isolated bronchial rings after pretreatment with beta 2-adrenoceptor agonists. Additionally, the influence of pretreatment with dexamethasone on desensitization was studied. 2. The effect of beta 2-agonist incubation alone and after coincubation with dexamethasone on density and affinity of beta-adrenoceptors was investigated by radioligand binding experiments. 3. In human isolated bronchi, isoprenaline induces a time- and concentration-dependent beta-adrenoceptor desensitization as judged from maximal reduction in potency by a factor of 7 and reduction of 73 +/- 4% in efficacy of isoprenaline to relax human bronchial smooth muscle. 4. After an incubation period of 60 min with 100 mumol l-1 terbutaline, a significant decline in its relaxing efficacy (81 +/- 8%) and potency (by a factor 5.5) occurred. 5. Incubation with 30 mumol l-1 isoprenaline for 60 min did not impair the maximal effect of a subsequent aminophylline response but led to an increase in potency (factor 4.4). 6. Coincubation of dexamethasone with isoprenaline (120 min; 30 mumol l-1) preserved the effect of isoprenaline on relaxation (129 +/- 15%). 7. In radioligand binding experiments, pretreatment of lung tissue for 60 min with isoprenaline (30 mumol l-1) resulted in a decrease in beta-adrenoceptor binding sites (Bmax) to 64 +/- 1.6% (P < 0.05), while the antagonist affinity (KD) for [3H]-CGP-12177 remained unchanged. 8. In contrast, radioligand binding studies on lung tissue pretreated with either dexamethasone (30 mumol l-1) or isoprenaline (30 mumol l-1) plus dexamethasone (30 mumol l-1) for 120 min did not lead to a significant change of Bmax (160 +/- 22.1% vs 142.3 +/- 28.7%) or KD (5.0 nmol l-1 vs 3.5 nmol l-1) compared to the controls. 9. In conclusion, pretreatment of human bronchi with beta-adrenoceptor agonists leads to functional desensitization and, in lung tissue, to down-regulation of beta-adrenoceptors. This effect can be counteracted by additional administration of dexamethasone. Our model of desensitization has proved useful for the identification of mechanisms of beta-adrenoceptor desensitization and could be relevant for the evaluation of therapeutic strategies to counteract undesirable effects of long-term beta-adrenoceptor stimulation.
Interesting read, but hypothetical at this point. If anyone has used it or has any other input, please contribute.
