개 하부식도괄약근의 비아드레날린성, 비콜린성 이완반응에 있어서 Cyclic Nucleotide의 역할

• 영문명: Regulatory Role of Cyclic Nucleotides in Non-Adrenergic Non-Cholinergic Relaxation of Lower Esophageal Sphincter from Dogs
• 발행기관: 대한생리학회-대한약리학회
• 저자명: 김영태(Young Tae Kim) 임병용(Byung Yong Rhim)
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제1권 제3호, 303~313쪽, 전체 11쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 1997.01.01

영문 초록

The role of the lower esophageal sphincter(LES) is characterized by the ability to maintain tone and to relax allowing the passage of a bolus. It is known that LES relaxation during swallowing may be induced by the cessation of the tonic neural excitation and the activation of non-adrenergic, non-cholinergic(NANC) inhibitory neurons. Furthermore, it is generally accepted that the relaxation of the smooth muscle is mediated primarily by the elaboration of adenosine 3 ,5 -cyclic monophosphate(cyclic AMP) and guanosine 3 ,5 -cyclic monophosphate(cyclic GMP) via activation of adenylate cyclase and guanylate cyclase, respectively. It is thus possible that cyclic nucleotides might be a second messenger involved in neural stimulation-induced relaxation of LES, although a relationship between relaxation and changes in cyclic nucleotides after neural stimulation has not been established. The present study was performed to define the participation of cyclic nucleotides in the relaxation of LES of dog in response to neural stimulation. Electrical field stimulation(EFS) caused relaxation of the canine isolated LES strips in a frequency-dependent manner, which was eliminated by pretreatment with tetrodotoxin(1 ㄍM), but not by atropine(100 ㄍM), guanethidine(100 ㄍM) and indomethacin(10 ㄍM). The nitric oxide synthase inhibitors, N^G-nitro-L-arginine, N^G-nitro-L-arginine methyl ester and N^G-monomethyl-L-arginine inhibited EFS- induced relaxation. Additions of sodium nitroprusside, a nitrovasodilator and forskolin, a direct adenylate cyclase stimulant, caused a dose-dependent relaxation of LES smooth muscle. Effects of sodium nitroprusside and forskolin were selectively blocked by the corresponding inhibitors, methylene blue for guanylate cyclase and N- ethylmaleimide(NEM) for adenylate cyclase, respectively. Dibutyryl cyclic AMP and dibutyryl cyclic GMP caused a concentration-dependent relaxation of the LES smooth muscle tone, which was not blocked by NEM or methylene blue, respectively. However, both NEM and methylene blue caused significant antagonism of the relaxation in LES tone in response to EFS. EFS increased the tissue cyclic GMP content by 124%, whereas it did not affect the tissue level of cyclic AMP. Based on these results, it is suggested that one of the components of canine LES smooth muscle relaxation in response to neural stimulation is mediated by an increase of cyclic GMP via the activation of guanylate cyclase. Additionally, an activation of cyclic AMP generation system was, in part, involved in the EFS-induced relaxation.

키워드

Lower esophageal sphincter Cyclic AMP Cyclic GMP Non-adrenergic non-cholinergic relaxation Nitric oxide