A β1- and β2-AR agonist
Isoprenaline HCl is an agonist of β-adrenergic receptor [1].
The adrenergic receptors are a class of G protein-coupled receptors that are targets of norepinephrine and epinephrine. When reacting with epinephrine, β-adrenergic receptor causes vasodilation.
In human umbilical vein endothelial cells (HUVECs), isoprenaline (100 nM) significantly increased the expression of connexins Cx43 and also increased Cx40 and Cx37. Also, isoprenaline increased the number of coupling cells. Isoprenaline enhanced the formation of branches and complex tube networks [2].
In the isolated field stimulated rat vas deferens, isoprenaline inhibited contractions with EC50 value of 45.6 nM. In tissues in which β 2-adrenoreceptors were maximally blocked by timolol, isoprenaline inhibited contractility with EC50 value of 1.5 μM [1]. In CFW mice, IPR caused the maximal proliferative response of bone marrow cells and increased erythropoietic activity. These results suggested that isoprenaline activated beta-adrenergic receptor, which then increased the proliferative and differentiation activities of hemopoietic stem cells [3].
异丙肾上腺素盐酸盐是β肾上腺素能受体的激动剂[1]。
肾上腺素能受体是一类G蛋白偶联受体，是去甲肾上腺素和肾上腺素的靶点。当与肾上腺素反应时，β肾上腺素能受体会引起血管扩张。
在人脐静脉内皮细胞（HUVECs）中，异丙肾上腺素（100 nM）显著增加了连结蛋白Cx43的表达，并且还增加了Cx40和Cx37的表达。此外，异丙肾上腺素增加了连接细胞的数量。异丙肾上腺素促进了分支和复杂的管网形成[2]。
在离体刺激的大鼠输精管中，异丙肾上腺素以EC50值为45.6 nM抑制了收缩。在β2肾上腺素能受体被吡咯烷脂全阻滞的组织中，异丙肾上腺素以EC50值为1.5 μM抑制了收缩[1]。在CFW小鼠中，异丙肾上腺素引起了骨髓细胞的最大增殖反应并增加了红细胞生成活性。这些结果表明，异丙肾上腺素激活了β肾上腺素能受体，从而增加了造血干细胞的增殖和分化活性[3]。
参考文献:
[1].? Lotti VJ, Cerino D, Kling P. Characterization of the adrenoreceptor activities of isoprenaline in the field stimulated rat vas deferens: selective supersensitivity to beta 2-mediated responses following reserpine treatment. J Auton Pharmacol, 1982, 2(3): 169-174.
[2].? Dhein S, Gaertner C, Georgieff C, et al. Effects of isoprenaline on endothelial connexins and angiogenesis in a human endothelial cell culture system. Naunyn Schmiedebergs Arch Pharmacol, 2015, 388(1): 101-108.
[3].? Lipski S. Effect of beta-adrenergic stimulation by isoprenaline on proliferation and differentation of mouse bone marrow cells in vivo. Pol J Pharmacol Pharm, 1980, 32(3): 281-287.
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Cell experiment: |
Cells are seeded in 24-well culture dishes at a density of 2 to 5×104 cells per well. Experiments are performed after 3 to 5 days in culture when cells has reached confluence. Culture medium is aspirated and replaced by 0.5 mL of PBS containing the pharmacological agents. Treatments are performed in quadruplicate at 37°C. The type 3, 4 and 5 PDE inhibitors cilostamide (10 gM), rolipram (10 pM) and DMPPO (10 gM), respectively, are incubated with cells for 30 min before addition of adenylate or guanylate cyclase activators. Cyclic GMP and cyclic AMP are respectively increased in RASMC by stimulation of particulate guanylate cyclase with ANF (50 nM for 10 min) or fl-adrenoceptors with isoprenaline (5 nm for 5 min). At the end of the incubation period, the medium is removed and intracellular cyclic nucleotides are extracted by two ethanolic (65%) ishes at 4°C for 5 min. Ethanolic extracts are pooled, evaporated to dryness by a Speed-Vac system. The dried extract is dissolved in a suitable amount of assay buffer and cyclic nucleotide levels are measured by scintillation proximity assay. |
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参考文献: [1]. Degerman E, et al. Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation. Proc Natl Acad Sci U S A. 1990 Jan;87(2):533-7 |
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