TY - JOUR
T1 - Myogenic effect of SP-1f and SP-1h two novel 3-adrenoceptor (3-AR) agonists in human colonic circular smooth muscle
AU - Maselli, Maria Antonietta
AU - Trisolini, Piero
AU - Ignazzi, Antonia
AU - Notarnicola, Maria
AU - Lorusso, Dionigi
AU - Pezzolla, Francesco
AU - Iacobazzi, Dominga
AU - Scilimati, Antonio
AU - Perrone, Maria Grazia
PY - 2014/1/15
Y1 - 2014/1/15
N2 - The effect of two novel 3-adrenoceptor (3-AR) agonists SP-1f and SP-1h on human colon circular smooth muscle contractility and 3-AR mRNA expression have been determined. 3-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 (1-, 2- and 3-AR antagonists, respectively). (-)-Isoprenaline concentration-dependently relaxed circular muscle strips with an EC 50=0.32±0.06 μM. Such an effect was antagonized either by the contemporaneously presence of Betaxolol and ICI 11,855 [(-)-isoprenaline EC50=1.75±0.35 μM, pKB=7.88±0.10] or by Betaxolol, ICI 11,855 and SR 59230A [(-)-isoprenaline EC50=3. 49±0.38 μM, pKB=8.51±0.14]. Besides, SP-1f and SP-1h concentration-dependently relaxed circular muscle strips with an EC 50=0.35±0.07 μM and 0.45±0.12 μM, respectively. These values remained unchanged by blocking the 1- and 2-AR. The presence of SR 59230A antagonized the relaxing effect of SP-1f (EC50=3.51±0.94 μM, pKB=8.93±0.16) and did not modify the SP-1h relaxing potency. In colon circular smooth muscle and in mucosa, 3-AR mRNA expression levels were found to be 0.39±0.70 and 0.26±0.12 (P3-adrenoceptor functional role in the human colon and the crucial contribution of SP-1f to the control of the gut dysmotility.
AB - The effect of two novel 3-adrenoceptor (3-AR) agonists SP-1f and SP-1h on human colon circular smooth muscle contractility and 3-AR mRNA expression have been determined. 3-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 (1-, 2- and 3-AR antagonists, respectively). (-)-Isoprenaline concentration-dependently relaxed circular muscle strips with an EC 50=0.32±0.06 μM. Such an effect was antagonized either by the contemporaneously presence of Betaxolol and ICI 11,855 [(-)-isoprenaline EC50=1.75±0.35 μM, pKB=7.88±0.10] or by Betaxolol, ICI 11,855 and SR 59230A [(-)-isoprenaline EC50=3. 49±0.38 μM, pKB=8.51±0.14]. Besides, SP-1f and SP-1h concentration-dependently relaxed circular muscle strips with an EC 50=0.35±0.07 μM and 0.45±0.12 μM, respectively. These values remained unchanged by blocking the 1- and 2-AR. The presence of SR 59230A antagonized the relaxing effect of SP-1f (EC50=3.51±0.94 μM, pKB=8.93±0.16) and did not modify the SP-1h relaxing potency. In colon circular smooth muscle and in mucosa, 3-AR mRNA expression levels were found to be 0.39±0.70 and 0.26±0.12 (P3-adrenoceptor functional role in the human colon and the crucial contribution of SP-1f to the control of the gut dysmotility.
KW - -Adrenoceptor (-AR)
KW - Agonist
KW - Human colon motility
UR - http://www.scopus.com/inward/record.url?scp=84890814696&partnerID=8YFLogxK
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U2 - 10.1016/j.ejphar.2013.11.010
DO - 10.1016/j.ejphar.2013.11.010
M3 - Article
C2 - 24275352
AN - SCOPUS:84890814696
VL - 723
SP - 62
EP - 66
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -