Purinergic mechanisms in the nervous system: the role of adenosine triphosphate in the migraine pathophysiology

Year 2016, , 132 - 152, 01.05.2016

Erkan Kılınç

https://doi.org/10.5505/abantmedj.2016.98250

Abstract

Notwithstanding that adenosine 5'-triphosphate ATP is an intracellular energy source, it is an important neurotransmitter and co-transmitter which play a role in purinergic signaling when it get out of the cell. Extracellular ATP is a signaling molecule in the most area of the body and it shows its effects via ionotropic P2X and metabotropic P2Y receptors in the central and peripheral nervous system. These purinergic receptors activated by ATP and other nucleotides demonstrate a wide distribution throughout the body. It is well established nowadays that ATP has function as a neurotransmitter in the central and peripheral nervous system and purinergic signaling plays a role in many physiological process and additionally in the pathological conditions such as pain, migraine and inflammation. Recently studies have showed that ATP has a role in initiation and propagation of somatic and visceral pains. ATP is able to initiate periferal pain signals via P2X3 and P2X2/3 receptors which are located primary afferent nerve terminals. When ATP activate these receptors, pain signals are produced by membrane depolarization via cation inflow to the cell. Transmission of pain signals from periferal to central are mediated by P2X2, P2X3 and P2X6 receptors which are located second order neurons. Although it has been known that main process in initiation of migraine pain is activation of the trigeminovascular system, pathophysiology of migraine is not yet completely understood. It has been claimed by studies recently that ATP may play a key role via its purinoceptors in migraine headache as well like somatic pains. In the present review, functions of extracellular ATP and its purinoceptors in the migraine pathophysiology and new treatment approaches were discussed.

Keywords

Adenosine triphosphate, pain, trigeminovascular system, migraine, purinergic receptors.

Sinir Sisteminde Pürinerjik Mekanizmalar: Adenozin Trifosfatın Migren Patofizyolojisindeki Rolü

Abstract

Adenozin 5'-trifosfat ATP hücre içi enerji kaynağı olmasının yanında hücre dışına çıktığında pürinerjik haberleşmede rol oynayan önemli bir nörotansmitter ve ko-transmitterdir. Vücudun birçok bölümünde bir sinyal molekülü olan ekstrasellüler ATP, merkezi ve periferik sinir sisteminde etkisini iyonotropik P2X ve metabotropik P2Y reseptörleri aracılığı ile gösterir. ATP ve diğer nükleotitlerin aktive ettiği bu pürinerjik reseptörler tüm vücut boyunca dağılım gösterir. ATP' nin merkezi ve periferik sinir sisteminde bir nörotransmitter olarak işlevinin olduğu ve pürinerjik haberleşmenin birçok fizyolojik olayda ve ayrıca ağrı, migren ve inflamasyon gibi patofizyolojik durumlarda rol oynadığı günümüzde daha iyi bilinmektedir. Son zamanlarda yapılan çalışmalar ATP' nin somatik ve viseral ağrıların başlatılmasında ve iletilmesinde rolü olduğunu göstermektedir. ATP primer afferent sinir terminallerinde bulunan P2X3 ve P2X2/3 reseptörleri aracılığı ile periferik ağrı sinyallerini başlatabilmektedir. ATP bu reseptörleri aktive ettiğinde hücre içine hızlı bir katyon girişi ile membran depolarize olmakta ve ağrı sinyalleri oluşmaktadır. Ağrı sinyallerinin periferden merkeze aktarılmasına ise ikinci sıra nöronlarında bulunan P2X2, P2X3 ve P2X6 reseptörleri aracılık etmektedir. Migren ağrısının başlamasındaki asıl olayın trigeminovasküler sistemin aktivasyonu olduğu bilinmesine rağmen migren patofizyolojisi henüz anlaşılamamıştır. Son zamanlarda yapılan çalışmalarla somatik ağrılarda olduğu gibi bir viseral ağrı olan migren baş ağrısında da ATP' nin pürinoseptörleri aracılığı ile önemli bir rol oynayabileceği ileri sürülmektedir. Sunulan derlemede bir nörotransmitter olarak ekstrasellüler ATP ve pürinoseptörlerinin migren patofizyolojisindeki işlevleri ve yeni tedavi yaklaşımları tartışılmıştır.

Keywords

Adenozin trifosfat, ağrı, trigeminovasküler sistem, migren, pürinerjik reseptörler.

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