European Journal of Pharmacology 2014-01-15

Myogenic effect of SP-1f and SP-1h two novel β3-adrenoceptor (β3-AR) agonists in human colonic circular smooth muscle.

Maria Antonietta Maselli, Piero Trisolini, Antonia Ignazzi, Maria Notarnicola, Dionigi Lorusso, Francesco Pezzolla, Dominga Iacobazzi, Antonio Scilimati, Maria Grazia Perrone

文献索引：Eur. J. Pharmacol. 723 , 62-6, (2014)

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摘要

The effect of two novel β3-adrenoceptor (β3-AR) agonists SP-1f and SP-1h on human colon circular smooth muscle contractility and β3-AR mRNA expression have been determined. β3-AR is ascertained co-participates to the control of the gut motility. Isometric tension on human colon muscle strips was measured in response to increasing concentrations of SP-1f, SP-1h and (-)-isoprenaline, alone and in the presence of Betaxolol, ICI 11,855 and SR 59230A (β1-, β2- and β3-AR antagonists, respectively). (-)-Isoprenaline concentration-dependently relaxed circular muscle strips with an EC50=0.32±0.06μM. Such an effect was antagonized either by the contemporaneously presence of Betaxolol and ICI 11,855 [(-)-isoprenaline EC50=1.75±0.35μM, pKB=7.88±0.10] or by Betaxolol, ICI 11,855 and SR 59230A [(-)-isoprenaline EC50=3.49±0.38μM, pKB=8.51±0.14]. Besides, SP-1f and SP-1h concentration-dependently relaxed circular muscle strips with an EC50=0.35±0.07μM and 0.45±0.12μM, respectively. These values remained unchanged by blocking the β1- and β2-AR. The presence of SR 59230A antagonized the relaxing effect of SP-1f (EC50=3.51±0.94μM, pKB=8.93±0.16) and did not modify the SP-1h relaxing potency. In colon circular smooth muscle and in mucosa, β3-AR mRNA expression levels were found to be 0.39±0.70 and 0.26±0.12 (P<0.05), respectively. Such results provide further evidence of the β3-adrenoceptor functional role in the human colon and the crucial contribution of SP-1f to the control of the gut dysmotility. © 2013 Published by Elsevier B.V.