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Eur J Pharmacol. 2014 Jan 15;723:62-6. doi: 10.1016/j.ejphar.2013.11.010. Epub 2013 Nov 22.

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

Author information

  • 1Experimental Pharmacology Laboratory, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
  • 2Nutritional Biochemistry Laboratory, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
  • 3Surgery Department, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
  • 4Department of Pharmacy & Pharmaceutical Sciences, University of Bari "A. Moro", Via Orabona 4, 70125 Bari, Italy.
  • 5Department of Pharmacy & Pharmaceutical Sciences, University of Bari "A. Moro", Via Orabona 4, 70125 Bari, Italy. Electronic address: antonio.scilimati@uniba.it.

Abstract

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.

KEYWORDS:

Agonist; Human colon motility; β(3)-Adrenoceptor (β(3)-AR)

PMID:
24275352
[PubMed - indexed for MEDLINE]
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