title: Myogenic effect of SP-1f and SP-1h two novel β3-adrenoceptor (β3-AR) agonists in human colonic circular smooth muscle.
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.
authors.affiliation: Experimental Pharmacology Laboratory, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Maselli
authors.affiliation: Experimental Pharmacology Laboratory, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Trisolini
authors.affiliation: Experimental Pharmacology Laboratory, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Ignazzi
authors.affiliation: Nutritional Biochemistry Laboratory, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Notarnicola
authors.affiliation: Surgery Department, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
authors.forename: Dionigi
authors.initials: D
authors.lastname: Lorusso
authors.affiliation: Surgery Department, Scientific Institute of Gastroenterology "S. de Bellis", 70013 Castellana Grotte, Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pezzolla
authors.affiliation: Department of Pharmacy & Pharmaceutical Sciences, University of Bari "A. Moro", Via Orabona 4, 70125 Bari, Italy.
authors.forename: Dominga
authors.initials: D
authors.lastname: Iacobazzi
authors.affiliation: Department of Pharmacy & Pharmaceutical Sciences, University of Bari "A. Moro", Via Orabona 4, 70125 Bari, Italy. Electronic address: antonio.scilimati@uniba.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Scilimati
authors.affiliation: Department of Pharmacy & Pharmaceutical Sciences, University of Bari "A. Moro", Via Orabona 4, 70125 Bari, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Perrone
mesh_terms: D015078:2-Hydroxyphenethylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology*; D000368:Aged; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011422:Propionates / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D013237:Stereoisomerism
chemical_list: C000592142:2-(4-(2-(2-hydroxy-2-phenylethylamino)ethyl)phenoxy)propanoic acid; D058673:Adrenergic beta-3 Receptor Antagonists; D011422:Propionates; D012333:RNA, Messenger; D022702:Receptors, Adrenergic, beta-3; D015078:2-Hydroxyphenethylamine; D007545:Isoproterenol
keywords: Agonist; Human colon motility; β(3)-Adrenoceptor (β(3)-AR)