Oreksinler (hipokretinler): Obezite tedavisinde yeni hedef moleküller

Amaç: Oreksin-A ve oreksin-B, 130 amino asidli prekürsör prepro-oreksinin proteolizi sonucu oluşan iki peptiddir. Bu derlemenin amacı, nispeten yeni tanımlanan bu nörotransmitterlerin iştahın düzenlenmesindeki rollerinin ve katkıda bulundukları diğer işlevlerin özetlenmesidir. Ana bulgular: İmmunoreaktif lifleri beyinde geniş ölçüde dağılan oreksinlerin şimdiye kadar iki reseptörü, OX1 ve OX2, tanımlanmıştır. Oreksin-A, OX1 ve OX2 reseptörlerine eşit etkinlikte, oreksin-B ise OX2 reseptörüne yaklaşık 10 kat daha selektiftir. Oreksin-A ve oreksin-B hipotalamusta ve santral sinir sisteminin diğer bölgelerinde, adrenal bezde ve ince barsakta gösterilmiştir. OX1 reseptörü esas olarak hipotalamus, locus coeruleus ve omurilikte tanımlanmıştır. OX2 reseptörü ise hipotalamus, korteks, omurilik ve bazı beyin nukleuslarında gösterilmiştir. Sonuç: Oreksinler, beslenme davranışı dışında, enerji dengesi, uyku-uyanıklık döngüsü, susama, ağrı, kardiyovasküler ve nörohormonal çeşitli işlevlere katılmaktadır.

Orexins (hipocretins): Novel target molecules in obesity treatment

Objective: Orexin A and orexin B are two peptides derived from proteolysis of a 130 amino acid precursor prepro-orexin. The aim of this review was to summarize role of these recently described neurotransmitters in regulation of appetite and other functions which they contribute to. Main findings: Immunoreactive fibers of orexins are present widespread in brain and two receptors of orexins, OX1 and OX2, are described so far. Orexin-A is equipotent at OX1 and OX2 receptors, whilst orexin-B displays 10 fold selectivity for OX2 receptor. Orexin-A and orexin-B are demonstrated in hypothalamus and other regions of central nervous system and also in adrenal gland and small intestine. OX1 receptor is defined mainly in the hypothalamus, locus coeruleus and spinal cord. OX2 receptor is presented in hypothalamus, cortex, spinal cord and a few brain nuclei. Conclusion: Except of feeding behavior, several functions are affected by orexins such as energy homeostasis, sleep-wake cycle, drinking, nociception, cardiovascular and neurohumeral process.

Kaynakça

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