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Chemical Compound Review

Proternol L     4-[(1R)-1-hydroxy-2-(propan- 2...

Synonyms: SureCN4166, CHEMBL460574, AG-E-96625, AC1Q7ABO, LS-42867, ...
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Disease relevance of l-Isoproterenol

  • Comparatively low levels of EP may be enough to induce syncope during tilting with ISP compared with tilting alone [1].
  • 6. Pre-treatment of the myocytes with pertussis toxin (0.5 microg ml-1, 4-6 h at 37 degrees C) eliminated the inhibitory effect of DEANO (100 microM) on ICa,L, in the presence of either Iso (0.01 and 1 nM) or IBMX (10-80 microM) [2].
  • Partial inhibition of mitochondrial function with nanomolar concentrations of FCCP or myxothiazol mimicked the effect of hypoxia on cellular superoxide and the sensitivity of I(Ca-L) to Iso [3].
  • TG-F mice showed LV hypertrophy without dilatation and only a small reduction of basal fractional shortening (FS) and response to isoproterenol (Iso) [4].
  • Forty-minute myocardial ischemia (MI) and 24-h reperfusion (R) further increased NO production and peroxynitrite formation and resulted in an enlarged infarct size in mice receiving chronic ISO stimulation [5].

Psychiatry related information on l-Isoproterenol


High impact information on l-Isoproterenol

  • These results were reflected in the absence of an effect of CCh on the positive inotropic effect of ISO in eNOSnull myocytes [7].
  • Nevertheless, the pharmacologic nitric oxide donors 3-morpholino-sydnonimine and S-nitroso-acetyl-cystein increased cGMP generation and suppressed ISO-augmented ICa-L in eNOSnull cells, suggesting that the signal transduction pathway(s) downstream of eNOS remained intact [7].
  • Sarcomere shortening velocity was measured as an index of contractility under four experimental conditions: at baseline, after adding isoproterenol (ISO; 1 nmol/L), after an NOS inhibitor (N pi-nitro-L-arginine methyl ester [L-NAME], 0.1 nmol/L), and after L-NAME plus ISO [8].
  • LVFS and LVEF values in transgenic mice during isoproterenol (ISO, 0.02 micrograms/kg per minute) infusion were higher than the values in control mice (LVFS, 68 +/- 4% versus 48 +/- 3%; LVEF, 96 +/- 1% versus 86 +/- 3%; P < .05) [9].
  • In three transgenic mice with heart rates held constant, LV dP/dt rose by 33 +/- 2% with ISO (0.02 micrograms/kg per minute) and by only 13 +/- 2% in three wild-type control mice (P < .01) [9].

Chemical compound and disease context of l-Isoproterenol


Biological context of l-Isoproterenol

  • Therefore, translocation of the TG lipase may explain, at least partially, the ISO-stimulated lipolysis in HSL-/- adipocytes [12].
  • Vasodilation following ISO was significantly attenuated in OSA patients compared with control subjects (-53.3 +/- 9.0% versus -64.7 +/- 10.3%, p = 0.049) [13].
  • In contrast, a transient (taudecay, approximately 200 s), supralinear up-regulation of Ih was observed upon coapplication of Iso and Bac that was larger than that observed with Iso alone [14].
  • Activation of beta-adrenergic receptors with (-)-isoproterenol (Iso) led to a small steady enhancement of Ih amplitude, whereas activation of GABAB receptors with (+/-)-Baclofen (Bac) reduced Ih, consistent with an up- and down-regulation of basal cAMP levels, respectively [14].
  • In good agreement with the latter result, the beta 1-adrenergic receptor (beta 1-AR)-selective antagonist CGP20712A had more effect on the Iso-stimulated AC activity in pre-obese than in lean pups (2-fold decreased in IC50) [15].

Anatomical context of l-Isoproterenol

  • The -log of the concentration giving 50% effect of l-isoprenaline on the right atrium was changed after doxorubicin pretreatment (8.33 +/- 0.04 versus 8.86 +/- 0.06 for control animals) [16].
  • To investigate beta AR coupling to G proteins, displacement by ISO of 125I-CYP binding was determined in aortic membranes in the presence and absence of the GTP analog guanosine-5'-(beta gamma-imido)triphosphate [Gpp(NH)p] (0.1 mM) [17].
  • The effect of L-isoprenaline was completely inhibited by the antagonist L-propranolol, confirming that the response was due to stimulation of beta-adrenergic receptors on the plasma membrane [18].
  • 1. Using front-surface fluorometry and fura-2-loaded medial strips of the porcine coronary artery, cytosolic Ca2+ concentration ([Ca2+]i) and tension development were simultaneously monitored in an attempt to determine the mechanisms of vasorelaxation induced by l-isoprenaline (Iso) [19].
  • Levels of the variant of the neuronal nitric oxide synthase (nNOS) that is restricted to Leydig cells, TnNOS, significantly increased in response to ISO, CRF, and EtOH over the time course of altered StAR/PBR concentrations [20].

Associations of l-Isoproterenol with other chemical compounds

  • Heart rates of transgenic mice were higher than those of control mice during ISO and NE infusion [9].
  • ACh (10 microM) inhibited the stimulatory effect of 3 nM Iso by 39 and 35% in WT and NOS3-KO myocytes, respectively [21].
  • In animals exposed to light from 30 min prior to injection to the time of sacrifice, ISO injections increased pineal melatonin content (P < 0.005, three-way ANOVA), which varied, depending on the specific time of injection (effect of time of night, P < 0.05, three-way ANOVA) [22].
  • However, pretreatment of the rats with N(w)nitro-arginine methylester, which blocked ISO-induced increases in TnNOS, neither restored the T response to human chorionic gonadotropin nor prevented the decreases in StAR and PBR [20].
  • Under chronic ISO stimulation, the up-regulated iNOS produced a significantly increased amount of nitric oxide (NO) and its byproduct, peroxynitrite, in the circulation and heart and subsequently resulted in an accelerated myocardial apoptosis [5].

Gene context of l-Isoproterenol

  • The results indicate that BK impairs human ASM cell responses to Iso, and the effect is largely mediated by B2 receptor-related COX product release via both COX isoforms and is independent of IL-1beta [23].
  • However, as previously seen with ISO, the presence of VIP did not allow the appearance of a somatostatin inhibitory response on cortical glial membranes [24].
  • Iso stimulated AP-1 binding activity to 203 +/- 19% of control within 2 h and stimulated protein synthesis to 145 +/- 17% of control [25].
  • These results demonstrate that the combination of the proinflammatory cytokines TNF-alpha and IFN-gamma reduce poststimulation (ISO or FSK) intracellular cAMP accumulation [26].
  • Pretreatment with either cytokine alone did not significantly affect ISO or FSK-induced intracellular cAMP accumulation, whereas the combination of TNF-alpha and IFN-gamma caused a significant (P < 0.05 compared with untreated cells) reduction [26].

Analytical, diagnostic and therapeutic context of l-Isoproterenol

  • The presence of erythropoietin during cell culture with L-isoprenaline had no effect on the desensitization or number of beta-adrenergic receptors [27].
  • Sympathetic denervation increased by 19-47% the basal- and ISO-stimulated activity of AC in these tissues, however, it had no effect on the phospholipase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)[28]
  • The concentration-response curve to ISO was shifted to the right in the HC group, compared with that in the control group [29].
  • The basal- and ISO-stimulated cAMP production in the sphincter was 4-fold as high as that of the dilator, and at 0.05 microM ISO the denervation supersensitivity for cAMP production in the sphincter increased by 118% as compared to 36% in the dilator [28].
  • Quarters of regenerated adrenocortical autotransplants, that are completely deprived of chromaffin cells, though displaying ALDO and B responses to IP and ACTH, were insensitive to PACAP [30].


  1. Triggering mechanism for neurally mediated syncope induced by head-up tilt test: role of catecholamines and response to propranolol. Kikushima, S., Kobayashi, Y., Nakagawa, H., Katagiri, T. J. Am. Coll. Cardiol. (1999) [Pubmed]
  2. G protein-mediated inhibitory effect of a nitric oxide donor on the L-type Ca2+ current in rat ventricular myocytes. Abi-Gerges, N., Fischmeister, R., Méry, P.F. J. Physiol. (Lond.) (2001) [Pubmed]
  3. Role of NAD(P)H oxidase in the regulation of cardiac L-type Ca2+ channel function during acute hypoxia. Hool, L.C., Di Maria, C.A., Viola, H.M., Arthur, P.G. Cardiovasc. Res. (2005) [Pubmed]
  4. Morphological and functional changes in cardiac myocytes isolated from mice overexpressing TNF-alpha. Janczewski, A.M., Kadokami, T., Lemster, B., Frye, C.S., McTiernan, C.F., Feldman, A.M. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  5. Chronic beta-adrenergic receptor stimulation induces cardiac apoptosis and aggravates myocardial ischemia/reperfusion injury by provoking inducible nitric-oxide synthase-mediated nitrative stress. Hu, A., Jiao, X., Gao, E., Koch, W.J., Sharifi-Azad, S., Grunwald, Z., Ma, X.L., Sun, J.Z. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  6. Estrogen influences stimulated water intake by ovariectomized female rats. Krause, E.G., Curtis, K.S., Davis, L.M., Stowe, J.R., Contreras, R.J. Physiol. Behav. (2003) [Pubmed]
  7. Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with targeted disruption of endothelial nitric oxide synthase. Han, X., Kubota, I., Feron, O., Opel, D.J., Arstall, M.A., Zhao, Y.Y., Huang, P., Fishman, M.C., Michel, T., Kelly, R.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  8. Role of myocyte nitric oxide in beta-adrenergic hyporesponsiveness in heart failure. Yamamoto, S., Tsutsui, H., Tagawa, H., Saito, K., Takahashi, M., Tada, H., Yamamoto, M., Katoh, M., Egashira, K., Takeshita, A. Circulation (1997) [Pubmed]
  9. Adverse effects of chronic endogenous sympathetic drive induced by cardiac GS alpha overexpression. Iwase, M., Bishop, S.P., Uechi, M., Vatner, D.E., Shannon, R.P., Kudej, R.K., Wight, D.C., Wagner, T.E., Ishikawa, Y., Homcy, C.J., Vatner, S.F. Circ. Res. (1996) [Pubmed]
  10. Gi/Go couple met-enkephalin to inhibition of cholinergic and beta-adrenergic stimulation of lacrimal secretion. Meneray, M.A., Fields, T.Y., Bennett, D.J. Cornea (2000) [Pubmed]
  11. Vasomotor responses in rats "intoxicated" with doxorubicin. Filippelli, W., Russo, S., Marrazzo, R., Marmo, M., Rossi, F. Res. Commun. Chem. Pathol. Pharmacol. (1994) [Pubmed]
  12. Lipolysis in the absence of hormone-sensitive lipase: evidence for a common mechanism regulating distinct lipases. Okazaki, H., Osuga, J., Tamura, Y., Yahagi, N., Tomita, S., Shionoiri, F., Iizuka, Y., Ohashi, K., Harada, K., Kimura, S., Gotoda, T., Shimano, H., Yamada, N., Ishibashi, S. Diabetes (2002) [Pubmed]
  13. Reduced alpha- and beta(2)-adrenergic vascular response in patients with obstructive sleep apnea. Grote, L., Kraiczi, H., Hedner, J. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  14. Pacemaker channels in mouse thalamocortical neurones are regulated by distinct pathways of cAMP synthesis. Frère, S.G., Lüthi, A. J. Physiol. (Lond.) (2004) [Pubmed]
  15. Early alterations in the brown adipose tissue adenylate cyclase system of pre-obese Zucker rat fa/fa pups: decreased G-proteins and beta 3-adrenoceptor activities. Charon, C., Krief, S., Diot-Dupuy, F., Strosberg, A.D., Emorine, L.J., Bazin, R. Biochem. J. (1995) [Pubmed]
  16. Cardioprotective properties of O-(beta-hydroxyethyl)-rutosides in doxorubicin-pretreated BALB/c mice. van Acker, S.A., Voest, E.E., Beems, D.B., Madhuizen, H.T., de Jong, J., Bast, A., van der Vijgh, W.J. Cancer Res. (1993) [Pubmed]
  17. Beta-adrenoceptor-G alpha S coupling decreases with age in rat aorta. Gurdal, H., Friedman, E., Johnson, M.D. Mol. Pharmacol. (1995) [Pubmed]
  18. Characteristics of the beta-adrenergic adenylate cyclase system of developing rabbit bone-marrow erythroblasts. Setchenska, M.S., Arnstein, H.R. Biochem. J. (1983) [Pubmed]
  19. Effects of isoprenaline on cytosolic calcium concentrations and on tension in the porcine coronary artery. Ushio-Fukai, M., Abe, S., Kobayashi, S., Nishimura, J., Kanaide, H. J. Physiol. (Lond.) (1993) [Pubmed]
  20. Activation of a neural brain-testicular pathway rapidly lowers Leydig cell levels of the steroidogenic acute regulatory protein and the peripheral-type benzodiazepine receptor while increasing levels of neuronal nitric oxide synthase. Herman, M., Rivier, C. Endocrinology (2006) [Pubmed]
  21. Muscarinic inhibitory and stimulatory regulation of the L-type Ca2+ current is not altered in cardiac ventricular myocytes from mice lacking endothelial nitric oxide synthase. Belevych, A.E., Harvey, R.D. J. Physiol. (Lond.) (2000) [Pubmed]
  22. A single injection of adrenergic agonists enhances pineal melatonin production in Turkish hamsters. Hong, S.M., Rollag, M.D., Ramirez, J., Stetson, M.H. J. Pineal Res. (1993) [Pubmed]
  23. Impaired cAMP production in human airway smooth muscle cells by bradykinin: role of cyclooxygenase products. Pang, L., Holland, E., Knox, A.J. Am. J. Physiol. (1998) [Pubmed]
  24. Vasoactive intestinal polypeptide receptors linked to an adenylate cyclase, and their relationship with biogenic amine- and somatostatin-sensitive adenylate cyclases on central neuronal and glial cells in primary cultures. Chneiweiss, H., Glowinski, J., Prémont, J. J. Neurochem. (1985) [Pubmed]
  25. Transcription activator protein 1 mediates alpha- but not beta-adrenergic hypertrophic growth responses in adult cardiomyocytes. Taimor, G., Schlüter, K.D., Best, P., Helmig, S., Piper, H.M. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  26. Ketamine inhibits the proinflammatory cytokine-induced reduction of cardiac intracellular cAMP accumulation. Hill, G.E., Anderson, J.L., Lyden, E.R. Anesth. Analg. (1998) [Pubmed]
  27. Independent activation of adenylate cyclase by erythropoietin and isoprenaline. Setchenska, M.S., Bonanou-Tzedaki, S.A., Arnstein, H.R. Mol. Cell. Endocrinol. (1988) [Pubmed]
  28. Effects of surgical sympathetic denervation on G-protein levels, alpha and beta-adrenergic receptors, cAMP production and adenylate cyclase activity in the smooth muscles of rabbit iris. Abdel-Latif, A.A., Akhtar, R.A., Zhou, C.J. Curr. Eye Res. (1995) [Pubmed]
  29. Dietary cholesterol affects sympathetic nerve function in rabbit hearts. Luo, T.Y., Wu, C.C., Liu, Y.B., Fu, Y.K., Su, M.J. J. Biomed. Sci. (2004) [Pubmed]
  30. Effects of pituitary adenylate-cyclase activating peptide (PACAP) on the rat adrenal secretory activity: preliminary in-vitro studies. Andreis, P.G., Malendowicz, L.K., Belloni, A.S., Nussdorfer, G.G. Life Sci. (1995) [Pubmed]
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