{"created":"2023-06-20T13:20:59.924916+00:00","id":1078,"links":{},"metadata":{"_buckets":{"deposit":"12f0b274-26ce-4ec9-a487-2a18173c8316"},"_deposit":{"created_by":1,"id":"1078","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"1078"},"status":"published"},"_oai":{"id":"oai:ir.soken.ac.jp:00001078","sets":["2:430:22"]},"author_link":["9255","9257","9256"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"加藤, 健一"}],"nameIdentifiers":[{}]}]},"item_1_creator_3":{"attribute_name":"フリガナ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"カトウ, ケンイチ"}],"nameIdentifiers":[{}]}]},"item_1_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"1995-03-23"}]},"item_1_degree_grantor_5":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"総合研究大学院大学"}]}]},"item_1_degree_name_6":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（学術）"}]},"item_1_description_12":{"attribute_name":"要旨","attribute_value_mlt":[{"subitem_description":"  The vas deferens smooth muscles play an essential role in the transport of spermatozoa and seminal emission from the testis to the urethra. However the mechanisms and regulatory factors of their contraction remaind in almost unknown. Thus, the contractile responses to neurotransmitters and excess external K+ in the guinea pig vas deferens have been studied in this thesis, with reference to cellular mechanisms of muscle innate contraction and relaxation. <br /> In Chapter 2, the basic contractile properties of the guinea pig vas deferens were investigated. Contractile responses to 100μM of noradrenaline (NA), adenosine triphosphate (ATP) and acetylcholine (ACh) were markedly altered by cooling the bath solution to 25℃. <br />  The NA-induced contractions were inhibited by prazosin but not by propranolol or yohimbin, indicating that the α1-adrenoceptor was dominant in the vas deferens. Pirenzepine (M1 antagonist) was more potent at inhibiting the ACh-induced contractions than antagonists of other muscarinic acetylcholine receptor subtypes, suggesting that the M1-muscarinic acetylcholine receptor was dominant. In the ATP responses, prior treatment with α, β-methylene ATP blocked ATP-induced contractile responses. Suramin, recently accepted as a P2x purinergic receptor blocker, attenuated contractions induced by a high concentrations of ATP (100μM) and completely abolished responses to the low concentration (10μM). <br /> NA-, ATP- and ACh-Induced contractlons were almost completely inhibited by deprivation of extracellular Ca2+, although nifedipine (L-type Ca2+ channel blocker, 10μM) did not inhibit completely the tonic phase of the NA- and ACh-induced contractions. The ATP-induced responses were inhibited by nifedipine. These data suggest that the NA-, ATP and ACh-induced contractions require the Influx of Ca2+ from the extracellular space, and that a nifedipine-insensitive pathway, presumably receptor-operative Ca2+-channels may contribute to the NA- and ACh-induced influx. <br />  In Chapter 3, the contractile responses to various concentrations of NA, ATP and ACh, and to excess external K+ in the epididymal, middle and prostatic portions of the guinea pig vas deferens were investigated by measuring the isotonic contraction and monitoring the Intracellular Ca2+ concentratlon ([Ca2+] i) using fura-2 fluorescence. In the epididymal portion, the contraction evoked by each of these agonists was biphasic comprising a transient followed by a tonic phase. In the middle portion, NA and ACh evoked biphasic contractions whereas the ATP-induced contraction was an almost monophasic transient. In contrast, in the prostatic portion, only transient contractions were evoked by ACh and ATP, while the NA-induced contracion was oscillatory. The maximum responses of tonic contraction to each of the neurotransmitters were largest in the epididymal portion, decreased in the middle and were almost absent in the prostatic portion. These regional differences in the contractile properties of the vas deferens were also evident upon stimulation with excess external K+. Such regional differences in contraction may involve regional differences in the Ca2+ homeostasis and/or the sensitivity of the contractile apparatus to intracellular Ca2+ ions.  The physiological relevance of the muscle innate regional contractile differences are unknown, however, it may contribute to the transport of spermatozoa by preventing back flow of the luminal contents, together with neuronal regulation. <br />  In Chapter 4, the effects of caffeine, 3-isobuty1-1-methylxanthine (IBMX) and forskolin on the NA-induced contraction were investigated. All drugs reduced the tonic contraction induced by NA in a concentration-dependent manner. Methylxanthines (caffeine and IBMX), by inhibiting the phosphodiesterase activity, cause an increase in intracellular cAMP concentration. Forskolin, by directly stimulating adenylate cyclase, also causes an increase in intracellular cAMP concentration. It is thus suggested that the reduction of NA-induced tonic contraction by these drugs may be mediated by cAMP. Pretreatment with these drugs inhibited the NA-induced contraction in a concentration-dependent manner, suggesting that cAMP affected not only the tonic phase but also the initiation of contraction evoked by NA. The effects of cAMP on NA-induced [Ca2+]i responses were investigated using the same protocol as for the contractile responses. Forskolin (10μM) did not have significant sustained effects on the NA-induced [Ca2+]i rise. In only the epididymal portion, a small transient [Ca2+]i decrease was observed. In contrast, pretreatment with forskolin (10μM) completely inhibited the [Ca2+]i increase. With excess external K+ stimulation, the same concentration of forskolin did not inhibit the [Ca2+]i increase. However, although sufficient increases of [Ca2+]i were observed, contractile responses to excess K+ were attenuated by pretreatment with forskolin. The inhibiting effect of forskolin suggests that relaxation mechanlsm(s) independent of decrease in [Ca2+]i exlsts in the smooth muscle and that cAMP may be involved in this Ca2+-independent relaxation. <br />  In summary, It is concluded as follows: <br />  1) The contractile responses to neurotransmitters were demonstrated to be potentiated by cooling the ambient temperature, whereas such hyprothemic potentiation was not observed for excess K+-induced contraction of guinea pig vas deferens.  2) The α 1-adrenergic, M1-muscarinic acetylcholine and P2x-purinergic receptors play essential roles in mediating the neurotransmitter-induced contractions of the vas deferens. <br />  3) Extracellular Ca2+ is necessary for the neurotransmitter-induced contraction of vas deferens. Nifedipine-insensitive Ca2+ influx pathways may be indispensably involved in the NA- and ACh-induced contractions. <br />  4) In the guinea pig vas deferens, there are regional differences in the <br />contractile responses to various neurotransmitters. These differences may involve variation in the mechanlsms of Ca2+  homeostasis and the sensitivity of contractile apparatus to intracellular Ca2+ ions. <br />  5) Increases of intracellular cAMP level may directly relax NA- and excess external K+-induced contractions by a mechanism independent of reduction in [Ca2+]i . Increased cAMP may also inhibit the NA-induced Ca2+ influx via nifedipine-insensitive Ca2+ pathways. thereby inhibiting NA-induced [Ca2+]i rise, and contraction.","subitem_description_type":"Other"}]},"item_1_description_18":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_1_description_7":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"総研大甲第147号","subitem_description_type":"Other"}]},"item_1_select_14":{"attribute_name":"所蔵","attribute_value_mlt":[{"subitem_select_item":"有"}]},"item_1_select_8":{"attribute_name":"研究科","attribute_value_mlt":[{"subitem_select_item":"生命科学研究科"}]},"item_1_select_9":{"attribute_name":"専攻","attribute_value_mlt":[{"subitem_select_item":"20 生理科学専攻"}]},"item_1_text_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_text_value":"1994"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"KATO, Kenichi","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲147_要旨.pdf","filesize":[{"value":"337.9 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"要旨・審査要旨 / Abstract, Screening Result","url":"https://ir.soken.ac.jp/record/1078/files/甲147_要旨.pdf"},"version_id":"9eeee882-cc24-4570-ad90-6f2d6717b7fd"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲147_本文.pdf","filesize":[{"value":"2.4 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/1078/files/甲147_本文.pdf"},"version_id":"f9a9968c-b6dc-4175-96da-144cdd43d187"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"モルモット輸精管の収縮特性","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"モルモット輸精管の収縮特性"},{"subitem_title":"Contractile Properties of the Guinea Pig VasDeferens","subitem_title_language":"en"}]},"item_type_id":"1","owner":"1","path":["22"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"1078","relation_version_is_last":true,"title":["モルモット輸精管の収縮特性"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:48:34.808870+00:00"}