Zinterol hydrochloride

Agonist effects of zinterol at the mouse and human beta(3)-adrenoceptor.[Pubmed:16601951]

Naunyn Schmiedebergs Arch Pharmacol. 2006 May;373(2):158-68.

The present study investigates the action of zinterol at beta(3)-adrenoceptors. We used mouse primary brown adipocytes and Chinese hamster ovary (CHO-K1) cells expressing the mouse or human beta(3)-adrenoceptor. Zinterol was a full agonist at increasing cyclic AMP levels in primary brown adipocytes (which express beta(1)- and beta(3)-adrenoceptors but not beta(2)-adrenoceptors), and this effect was almost totally abolished in adipocytes derived from beta(3)-adrenoceptor knock-out (KO) mice. Zinterol was also a full agonist at increasing another biological end-point, glucose uptake in brown adipocytes. This effect was reduced in adipocytes derived from beta(3)-adrenoceptor KO mice, with the remaining response sensitive to beta(1)-adrenoceptor antagonism. To determine whether the effect of zinterol on beta(3)-adrenoceptors in primary brown adipocytes can be replicated in a recombinant system, we used CHO-K1 cells expressing the mouse or human beta(3)-adrenoceptor. Zinterol was a full agonist at mouse and human receptors with respect to increasing cyclic AMP levels, with pEC(50) values similar to that of the selective beta(3)-adrenoceptor agonist (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2-d icarboxylate (CL316243) at the mouse receptor. At the human receptor, zinterol was more potent at increasing cyclic AMP levels than CL316243. In cytosensor microphysiometer studies, zinterol was a full agonist for increases in extracellular acidification rates at the mouse and human beta(3)-adrenoceptor. Therefore, we have shown that zinterol is a potent, high-efficacy beta(3)-adrenoceptor agonist at the endogenous mouse beta(3)-adrenoceptor in primary brown adipocytes and at the cloned mouse and human beta(3)-adrenoceptor expressed in CHO-K1 cells. Zinterol is therefore one of few beta-adrenoceptor agonists with high potency and efficacy at the human beta(3)-adrenoceptor.

Beta-2 adrenergic activation of L-type Ca++ current in cardiac myocytes.[Pubmed:9353357]

J Pharmacol Exp Ther. 1997 Nov;283(2):452-61.

The whole-cell patch-clamp and intracellular perfusion techniques were used for studying the effects of a beta-2 adrenergic receptor activation on the L-type Ca current (ICa) in frog ventricular myocytes. The beta-2 adrenergic agonist zinterol increased ICa in a concentration-dependent manner with an EC50 (i.e., the concentration of zinterol at which the response was 50% of the maximum) of 2.2 nM. The effect of zinterol was essentially independent of the membrane potential. The stimulatory effect of zinterol was competitively antagonized by ICI 118,551, a beta-2 adrenergic antagonist. The maximal stimulatory effect of zinterol was comparable in amplitude to the effect of a saturating concentration (1 or 10 microM) of isoprenaline, a nonselective beta adrenergic agonist. Moreover, 3-isobutyl-1-methylxanthine (100 microM), a nonselective phosphodiesterase inhibitor, or forskolin (10 microM), a direct activator of adenylyl cyclase, had no additive effects in the presence of 0.1 microM zinterol. Zinterol had a long lasting action on frog ICa because after washout of the drug, ICa returned to basal level with a time constant of 17 min. An application of acetylcholine (1 microM) during this recovery phase promptly reduced ICa back to its basal level suggesting a persistent activation of adenylyl cyclase due to a slow dissociation rate constant of zinterol from its receptor. Zinterol also increased ICa in rat ventricular and human atrial myocytes, and the maximal effect was obtained at 10 and 1 microM, respectively. In all three preparations, intracellular perfusion with 20 microM PKI(15-22), a highly selective peptide inhibitor of cAMP-dependent protein kinase, completely antagonized the stimulatory effect of zinterol on ICa. We conclude that beta-2 adrenergic receptor activation produces a strong increase in ICa in frog, rat and human cardiac myocytes which is due to stimulation of adenylyl cyclase and activation of cAMP-dependent phosphorylation.

Zinterol (MJ 9184) is a potent and selective β2-adrenoceptor agonist. Zinterol increases ICa in a concentration-dependent manner with an EC50 of 2.2 nM.

Zinterol hydrochloride,37000-20-7,MJ 9184,Natural Products,Adrenergic Receptor, buy Zinterol hydrochloride , Zinterol hydrochloride supplier , purchase Zinterol hydrochloride , Zinterol hydrochloride cost , Zinterol hydrochloride manufacturer , order Zinterol hydrochloride , high purity Zinterol hydrochloride