Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle
Since, in the human ureter, both β2- and β3-adrenoceptors mediate adrenergic-stimulation-induced relaxation, selective β2-/β3-adrenoceptor agonists might prove clinically useful for relieving ureteral colic and promoting stone passage. We evaluated the β-adrenoceptor subtype selectivity and ureteral...
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| Format: | Article |
| Language: | English |
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Elsevier
2003-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319326404 |
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| author | Yoshitaka Tomiyama Makoto Murakami Kohichi Hayakawa Katsuyoshi Akiyama Yoshinobu Yamazaki Masami Kojima Nobuo Shibata Masuo Akahane |
| author_facet | Yoshitaka Tomiyama Makoto Murakami Kohichi Hayakawa Katsuyoshi Akiyama Yoshinobu Yamazaki Masami Kojima Nobuo Shibata Masuo Akahane |
| author_sort | Yoshitaka Tomiyama |
| collection | DOAJ |
| description | Since, in the human ureter, both β2- and β3-adrenoceptors mediate adrenergic-stimulation-induced relaxation, selective β2-/β3-adrenoceptor agonists might prove clinically useful for relieving ureteral colic and promoting stone passage. We evaluated the β-adrenoceptor subtype selectivity and ureteral-relaxing efficacy of (-)-2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenyloxy]acetic acid (KUL-7211), a new β-adrenoceptor agonist, in vitro. In rat isolated organs, its selectivities, for inhibition of spontaneous uterine contraction (mediated via β2-adrenergic stimulation) and inhibition of colonic contraction (via β3-adrenergic stimulation) versus increase in atrial rate (via β1-adrenergic stimulation), were 56.3 and 242.2, respectively. KUL-7211 relaxed 80-mM-KCl-induced tonic contractions in both rabbit (pD2 value: 5.86 ± 0.13, whose ureteral relaxation is mediated via β2-adrenergic stimulation) and canine (pD2 value: 6.52 ± 0.16, via β3-adrenergic stimulation) isolated ureters in a concentration-dependent manner. These KUL-7211-induced relaxing effects were antagonized by ICI-118,551 (selective β2-adrenoceptor antagonist, pKB value: 8.91 ± 0.24) in the rabbit ureter and by bupranolol (non-selective β-adernoceptor antagonist, pKB value: 6.85 ± 0.12) in the canine ureter. KUL-7211 also reduced the spontaneous rhythmic contraction in a canine ureteral spiral preparation in a concentration-dependent manner, the pD2 value being 6.83 ± 0.20. These data clearly demonstrate that KUL-7211 selectively stimulates both ureteral β2- and β3-adrenoceptors and potently relaxes ureteral smooth muscle. KUL-7211 may be a novel and useful medication for relieving ureteral colic and promoting stone passage in urolithiasis patients. |
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| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-22T02:36:19Z |
| publishDate | 2003-01-01 |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-06363c70edbd48bf866b9f1e881497f32022-12-21T18:41:44ZengElsevierJournal of Pharmacological Sciences1347-86132003-01-01924411419Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth MuscleYoshitaka Tomiyama0Makoto Murakami1Kohichi Hayakawa2Katsuyoshi Akiyama3Yoshinobu Yamazaki4Masami Kojima5Nobuo Shibata6Masuo Akahane7Central Research Laboratory, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Nagano 399-8304, JapanCentral Research Laboratory, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Nagano 399-8304, JapanCentral Research Laboratory, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Nagano 399-8304, JapanCentral Research Laboratory, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Nagano 399-8304, JapanCentral Research Laboratory, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Nagano 399-8304, JapanCentral Research Laboratory, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Nagano 399-8304, JapanCentral Research Laboratory, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Nagano 399-8304, JapanCentral Research Laboratory, Kissei Pharmaceutical Co., Ltd., 4365-1, Kashiwabara, Hotaka, Nagano 399-8304, JapanSince, in the human ureter, both β2- and β3-adrenoceptors mediate adrenergic-stimulation-induced relaxation, selective β2-/β3-adrenoceptor agonists might prove clinically useful for relieving ureteral colic and promoting stone passage. We evaluated the β-adrenoceptor subtype selectivity and ureteral-relaxing efficacy of (-)-2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)phenyloxy]acetic acid (KUL-7211), a new β-adrenoceptor agonist, in vitro. In rat isolated organs, its selectivities, for inhibition of spontaneous uterine contraction (mediated via β2-adrenergic stimulation) and inhibition of colonic contraction (via β3-adrenergic stimulation) versus increase in atrial rate (via β1-adrenergic stimulation), were 56.3 and 242.2, respectively. KUL-7211 relaxed 80-mM-KCl-induced tonic contractions in both rabbit (pD2 value: 5.86 ± 0.13, whose ureteral relaxation is mediated via β2-adrenergic stimulation) and canine (pD2 value: 6.52 ± 0.16, via β3-adrenergic stimulation) isolated ureters in a concentration-dependent manner. These KUL-7211-induced relaxing effects were antagonized by ICI-118,551 (selective β2-adrenoceptor antagonist, pKB value: 8.91 ± 0.24) in the rabbit ureter and by bupranolol (non-selective β-adernoceptor antagonist, pKB value: 6.85 ± 0.12) in the canine ureter. KUL-7211 also reduced the spontaneous rhythmic contraction in a canine ureteral spiral preparation in a concentration-dependent manner, the pD2 value being 6.83 ± 0.20. These data clearly demonstrate that KUL-7211 selectively stimulates both ureteral β2- and β3-adrenoceptors and potently relaxes ureteral smooth muscle. KUL-7211 may be a novel and useful medication for relieving ureteral colic and promoting stone passage in urolithiasis patients.http://www.sciencedirect.com/science/article/pii/S1347861319326404 |
| spellingShingle | Yoshitaka Tomiyama Makoto Murakami Kohichi Hayakawa Katsuyoshi Akiyama Yoshinobu Yamazaki Masami Kojima Nobuo Shibata Masuo Akahane Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle Journal of Pharmacological Sciences |
| title | Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle |
| title_full | Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle |
| title_fullStr | Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle |
| title_full_unstemmed | Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle |
| title_short | Pharmacological Profile of KUL-7211, a Selective -Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle |
| title_sort | pharmacological profile of kul 7211 a selective adrenoceptor agonist in isolated ureteral smooth muscle |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319326404 |
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