Publication: Muskarinik asetilkolin reseptörlerinin dağılımı ve ilişkili sinyal ileti yolları
Abstract
Muskarinik reseptörler G protein kenetli reseptör ailesinin üyesidirler. Moleküler klonlama çalışmaları ile beş intronsuz gen tarafından kodlandığı ve beş farklı glikoproteini kodladığı belirlenmiştir. Muskarinik reseptör genleri türler arasında oldukça benzerlik göstermektedir. Muskarinik reseptörler (M1, M3, M5) ve (M2, M4) olmak üzere iki fonksiyonel kategoriye ayrılmaktadır: M1, M3, ve M5 reseptörleri öncelikle Gq/11 proteinleri aracılığı ile fosfolipaz C’yi aktive ederken M2, M4 reseptörleri Gi/o proteinleri aracılığıyla adenilat siklazı inhibe etmektedir. Muskarinik reseptörler merkezi ve periferal dokularda yaygın olarak bulunmaktadır. M1 reseptörleri önbeyinde özellikle hipokampus ve serebral korteksde, M2 reseptörleri kalp ve beyin kökünde, M3 reseptörleri düz kas, ekzokrin salgı bezleri ve serebral korteksde, M4 reseptörleri neostriatumda ve M5 reseptörleri substantia nigra’da bulunmaktadır. Merkezi sinir sisteminde fazla bulunan M1 reseptörleri asetilkolinle indüklenen MAP kinaz aktivasyonuna aracılık etmektedir. MAP kinaz hafıza için gereklidir. Beyin M2 reseptörleri “antinociseptive” etki için önemli rol oynamaktadır. Ayrıca M2 reseptörleri muskarinik asetilkolin reseptörü bağımlı bradikardi ve mide, trake ve idrar kesesi düz kaslarının agonistle uyarılması için gereklidir. M3 reseptörleri tükrük salgılanması, pupil daralması ve idrar kesesi detrüsör kasının kasılmasında fonksiyoneldir. Beyin M4 reseptörleri merkezi dopaminerjik cevapların ve periferal düz kas tonusunun düzenlenmesine katılmaktadır. M5 reseptörlerinin dopamin salınımının düzenlenmesine katıldığı bilinmektedir, fakat bu düzenlenme mekanizması henüz tam olarak anlaşılmamıştır. Muskarinik reseptörlerin kalp fonksiyon bozukluğu, Alzheimer, astım gibi hastalıklarda rolü olduğu belirtilmektedir. Muskarinik reseptörlerin çeşitli hücre ve dokularda belirlenmesi seçici ilaçların geliştirilmesinde önemlidir.
Muscarinic receptors are members of G protein coupled receptor family. Molecular cloning studies indicate five intronless genes that encode five muscarinic receptor glycoproteins. Muscarinic receptor genes are fairly similar between species. Muscarinic receptors mediate many cellular responses by activating second messenger systems through the action of G proteins. Muscarinic receptors are divided into two functional categories; M1, M3, and M5 receptors preferentially couple to the Gq/11 protein which activates phospholipase C, whereas M2 and M4 receptors preferentially couple to Gi/o protein, which inhibits adenylate cyclase activity. Muscarinic receptors are distributed widely in central and peripheral tissues. M1 receptors are found in the forebrain, especially in the hippocampus and cerebral cortex. M2 receptors are found heart and brainstem, M3 receptors are found in the smooth muscle, exocrine glands and cerebral cortex. M4 receptors are seen in the neo-striatum and M5 receptor mRNA is found in the substantia nigra. M2 receptors in the CNS are the main muscarinic acethylcholine receptors that mediate acethylcholine induced MAP kinase activation which is necessary for memory. The brain M2 receptors play important role for antinociception. In addition, M2 receptors are essential for muscarinic acethylcholine receptor-dependent bradycardia and agonist induced contraction of stomach, urinary bladder and trachea. M3 receptors are involved in salivary secretion, pupillary constriction and bladder detrusor contraction. Brain M4 receptors are participate in the modulation of central dopaminergic responses and regulate peripheral smooth muscle tone. M5 receptors may regulate dopamine release. But this regulation is not fully understood. Muscarinic receptors are involved in different pathological conditions such as heart failure, Alzheimer disease and asthma. Identification of muscarinic receptor subtypes expressed in various cells and tissues is important in the de-velopment of selective drugs.
Muscarinic receptors are members of G protein coupled receptor family. Molecular cloning studies indicate five intronless genes that encode five muscarinic receptor glycoproteins. Muscarinic receptor genes are fairly similar between species. Muscarinic receptors mediate many cellular responses by activating second messenger systems through the action of G proteins. Muscarinic receptors are divided into two functional categories; M1, M3, and M5 receptors preferentially couple to the Gq/11 protein which activates phospholipase C, whereas M2 and M4 receptors preferentially couple to Gi/o protein, which inhibits adenylate cyclase activity. Muscarinic receptors are distributed widely in central and peripheral tissues. M1 receptors are found in the forebrain, especially in the hippocampus and cerebral cortex. M2 receptors are found heart and brainstem, M3 receptors are found in the smooth muscle, exocrine glands and cerebral cortex. M4 receptors are seen in the neo-striatum and M5 receptor mRNA is found in the substantia nigra. M2 receptors in the CNS are the main muscarinic acethylcholine receptors that mediate acethylcholine induced MAP kinase activation which is necessary for memory. The brain M2 receptors play important role for antinociception. In addition, M2 receptors are essential for muscarinic acethylcholine receptor-dependent bradycardia and agonist induced contraction of stomach, urinary bladder and trachea. M3 receptors are involved in salivary secretion, pupillary constriction and bladder detrusor contraction. Brain M4 receptors are participate in the modulation of central dopaminergic responses and regulate peripheral smooth muscle tone. M5 receptors may regulate dopamine release. But this regulation is not fully understood. Muscarinic receptors are involved in different pathological conditions such as heart failure, Alzheimer disease and asthma. Identification of muscarinic receptor subtypes expressed in various cells and tissues is important in the de-velopment of selective drugs.