京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19565号 / 医博第4072号 / 新制||医||1013(附属図書館) / 32601 / 京都大学大学院医学研究科医学専攻 / (主査)教授 江藤 浩之, 教授 前川 平, 教授 髙折 晃史 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p>α₁- and α₂-Adrenoceptors are involved in various physiological events in the eye: blood flow regulation, aqueous humor dynamics and pupil regulation. The α₁- and α₂-adrenoceptors can be further subdivided into six subtypes (α_1A, α_1B, α_1D, α_2A , α_2B, and α_2C ). Currently available α1- and α₂-adrenergic drugs are not selective for the different subtypes and some ocular adrenergics have undesirable side-effects, both local and systemic. A better understanding of the subtype distribution in the eye would be useful when designing new drugs with greater efficacy and fewer adverse effects; this applies especially to the treatment of glaucoma. The purpose of the thesis was therefore to identify and localize the different subtypes of α₁- and α₂-adrenoceptors in the eye. </p><p>The identities of the α₁-adrenoceptor subtypes were studied in various parts of pig and albino rabbit eyes by radioligand binding. In the pig retina and in the albino rabbit iris, ciliary body and retina, mixed populations of α_1A- and α_1B-adrenoceptors were localized. In the rabbit choroid only the α_1A-adrenoceptor subtype was detected. </p><p>The α₂-adrenoceptor subtypes were also characterized by radioligand binding, in different parts of the pig eye. In the iris, ciliary body and choroid, only α_2A-adrenoceptors were localized, while in the retina, mostly α_2A-adrenoceptors and a minor population of α_2C-adrenoceptors were identified. High densities of α_2A-adrenoceptors were found in the ciliary body and choroid.</p><p>The effect of α₂-adrenoceptor agonists on the porcine ciliary artery was studied on a small-vessel myograph. α₂-Adrenoceptor agonists proved to be potent vasoconstrictors in the porcine ciliary artery and it was found that the vasoconstriction induced by brimonidine was mediated by the α_A-adrenoceptor.</p>

α1- and α2-Adrenoceptors are involved in various physiological events in the eye: blood flow regulation, aqueous humor dynamics and pupil regulation. The α1- and α2-adrenoceptors can be further subdivided into six subtypes (α1A, α1B, α1D, α2A , α2B, and α2C ). Currently available α1- and α2-adrenergic drugs are not selective for the different subtypes and some ocular adrenergics have undesirable side-effects, both local and systemic. A better understanding of the subtype distribution in the eye would be useful when designing new drugs with greater efficacy and fewer adverse effects; this applies especially to the treatment of glaucoma. The purpose of the thesis was therefore to identify and localize the different subtypes of α1- and α2-adrenoceptors in the eye. The identities of the α1-adrenoceptor subtypes were studied in various parts of pig and albino rabbit eyes by radioligand binding. In the pig retina and in the albino rabbit iris, ciliary body and retina, mixed populations of α1A- and α1B-adrenoceptors were localized. In the rabbit choroid only the α1A-adrenoceptor subtype was detected. The α2-adrenoceptor subtypes were also characterized by radioligand binding, in different parts of the pig eye. In the iris, ciliary body and choroid, only α2A-adrenoceptors were localized, while in the retina, mostly α2A-adrenoceptors and a minor population of α2C-adrenoceptors were identified. High densities of α2A-adrenoceptors were found in the ciliary body and choroid. The effect of α2-adrenoceptor agonists on the porcine ciliary artery was studied on a small-vessel myograph. α2-Adrenoceptor agonists proved to be potent vasoconstrictors in the porcine ciliary artery and it was found that the vasoconstriction induced by brimonidine was mediated by the αA-adrenoceptor.