Characterizations of the α1-adrenoceptor subtypes mediating contractions of the human internal anal sphincter.
Human internal anal sphincter (IAS) is contracted by α1-adrenoceptor stimulation and thus α1-adrenoceptor agonists may be useful in treating fecal incontinence. This study characterizes the contribution of α1-adrenoceptor subtypes in contraction of human IAS and to investigate the age-related risk of patients with fecal incontinence. IAS and inferior mesenteric artery (IMA), as a predictor of systemic arterial pressure, were obtained from 11 patients. Both muscle strips were assessed by isometric-contraction experiments using phenylephrine, further in IAS, in the presence of various subtype selective α1-adrenoceptor antagonists. Immunohistochemistry and gene expression studies were performed in the same samples. The mean pEC50 values with SEM of phenylephrine in IAS (6.30 ± 0.13) were higher than those of IMA (5.60 ± 0.10). Furthermore, the age-related pEC50 change of IAS was observed between age <70 and ≥70 (6.58 ± 0.13 and 6.07 ± 0.16, respectively (P < 0.05)). In IAS, rightward shift of the concentration-response curves of phenylephrine was observed with three α1-adrenoceptor antagonists. Each pKB value of silodosin, BMY-7378 and prazosin was 9.36 ± 0.53, 7.28 ± 0.20 and 8.89 ± 0.12, respectively. These pKB values and gene expression studies indicated that α1A-adrenoceptor subtypes predominantly contributed to human IAS contraction.
Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan. Electronic address: hiroyuki-owaki@naramed-u.ac.jp.
Hiroyuki
H
Owaki
Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Sotaro
S
Sadahiro
Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan; Department of Molecular Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Miyako
M
Takaki
D058646:Adrenergic alpha-1 Receptor Agonists / Q000627:therapeutic use; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001003:Anal Canal / Q000187:drug effects / Q000503:physiopathology*; D005242:Fecal Incontinence / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000235:genetics*; D008297:Male; D017537:Mesenteric Artery, Inferior / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology*; D012306:Risk
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine
Age-related response change; As a predictor of systemic arterial pressure; Comparison with inferior mesenteric artery; Fecal incontinence; Human internal anal sphincter; α(1)-adrenoceptor