Imidazolinski receptor

Imidazolinski receptori su primarni receptori na koje deluje klonidin i drugi imidazolini.^[1]^[2]^[3] Postoje tri glavne klase imidazolinskih receptora: I₁ je uključen u inhibiciju simpatičkog nervnog sistema radi snižavanja krvnog pritiska,^[4] I₂ ima još neizvesne funkcije, ali je uključen u nekoliko psihijatrijskih stanja,^[5]^[6] i I₃ reguliše lučenje insulina.^[7]

Klase уреди

Postoje tri klase imidazolinskih receptora:^[1]

I₁ receptor – posreduje simpato-inhibitorna dejstva imidazolina čime snižava krvni pritisak
I₂ receptor – sadrži alosterno mesto vezivanja monoaminske oksidaze; učestvuje u modulaciji bola i neuroprotekciji
I₃ receptor – reguliše sekreciju insulina iz pankreasnih beta ćelija

Aktivirani I₁-imidazolinski receptori iniciraju hidrolizu fosfatidilholina u DAG. Povišeni DAG nivoi zatim podstiču sintezu sekundarnih glasnika arahidonske kiseline i niza eikozanoida.^[8] Osim toga dolazi do inhibicije natrijum-vodonik antiportera, i indukovanja enzima kateholaminske sinteze. I₁-imidazolinski receptor se može grupisati u familiju neurocitokinskih receptora, pošto su njegovi signalni putevi slični sa putevima interleukina.^[8]

Selectivni ligandi уреди

Agonisti уреди

7-Me-marsanidin
Agmatin (endogeni neselektivni agonist, takođe se vezuje za NMDA, nikotinski i adrenoceptore)
Apraklonidin (I₁ selektivan)
Moksonidin
Rilmenidin
Klonidin obično se navodi da je alfa₂ agonist. Nedavni nalazi ukazuju da je agonist imidazolnog receptora (I₁).^[9]
S-23515
S-23757
LNP-509
MCPP (slab)
2-BFI (selektivan agonist I₂ receptora, kao i NMDA antagonist^[10] )
BU224 (selektivni agonist I₂ receptora, niske efikasnosti)
LNP-911^[11]

Antagonisti уреди

Efaroksan (neselektivan, vezuje se za I₁ receptor i α₂ adrenoceptor)
Idazoksan (neselektivan, vezuje se za I₂ receptor i α₂ adrenoceptor)
BU99006 (alkilirajući agens, inaktivira I₂ receptore)

Antagonisti imidazolinskog I₂ receptora reverzibilno blokiraju NMDA receptorom posreduvan Ca²⁺ influks^[12] i stoga mogu da inhibiraju ekscitotoksičnost.

Vidi još уреди

Reference уреди

^ ^а ^б Head GA, Mayorov DN (јануар 2006). „Imidazoline receptors, novel agents and therapeutic potential”. Cardiovasc Hematol Agents Med Chem. 4 (1): 17—32. PMID 16529547. doi:10.2174/187152506775268758. Архивирано из оригинала 14. 4. 2013. г.
^ Hamilton CA, Yakubu MA, Howie CA, Reid JL (1992). „Do Centrally-Acting Antihypertensive Drugs Act at Non-Adrenergic as well as Alpha-2 Adrenoceptor Sites?”. Clinical and Experimental Hypertension Part A Theory and Practice. 14 (5): 815—835. PMID 1327589. doi:10.3109/10641969209036221.
^ Hamilton CA, Yakubu MA, Jardine E, Reid JL (1991). „Imidazole binding sites in rabbit kidney and forebrain membranes”. J Auton Pharmacol. 11 (5): 277—83. PMID 1939285. doi:10.1111/j.1474-8673.1991.tb00325.x.
^ Regunathan, S; Reis, D J (април 1996). „Imidazoline Receptors and Their Endogenous Ligands”. Annual Review of Pharmacology and Toxicology. 36 (1): 511—544. PMID 8725400. doi:10.1146/annurev.pa.36.040196.002455.
^ Kawamura, Kazunori; Shimoda, Yoko; Kumata, Katsushi; Fujinaga, Masayuki; Yui, Joji; Yamasaki, Tomoteru; Xie, Lin; Hatori, Akiko; Wakizaka, Hidekatsu; Kurihara, Yusuke; Ogawa, Masanao; Nengaki, Nobuki; Zhang, Ming-Rong (април 2015). „In vivo evaluation of a new 18F-labeled PET ligand, [18F]FEBU, for the imaging of I2-imidazoline receptors”. Nuclear Medicine and Biology. 42 (4): 406—412. PMID 25583220. doi:10.1016/j.nucmedbio.2014.12.014.
^ GARCIA-SEVILLA, JESUS A.; ESCRIBA, PABLO V.; GUIMON, JOSE (јун 1999). „Imidazoline Receptors and Human Brain Disorders”. Annals of the New York Academy of Sciences. 881 (1 IMIDAZOLINE R): 392—409. Bibcode:1999NYASA.881..392G. PMID 10415944. S2CID 10081479. doi:10.1111/j.1749-6632.1999.tb09388.x.
^ Head, G.; Mayorov, D. (1. 1. 2006). „Imidazoline Receptors, Novel Agents and Therapeutic Potential”. Cardiovascular & Hematological Agents in Medicinal Chemistry. 4 (1): 17—32. PMID 16529547. doi:10.2174/187152506775268758.
^ ^а ^б Ernsberger P (јун 1999). „The I1-imidazoline receptor and its cellular signaling pathways”. Ann. N. Y. Acad. Sci. 881 (1): 35—53. PMID 10415895. doi:10.1111/j.1749-6632.1999.tb09339.x. Архивирано из оригинала 2009-01-08. г. Приступљено 2014-06-30.
^ Reis DJ, Piletz JE (новембар 1997). „The imidazoline receptor in control of blood pressure by clonidine and allied drugs” (pdf). Am. J. Physiol. 273 (5 Pt 2): R1569—71. PMID 9374795.
^ Han, Z; et al. „Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.”. PLoS One (2014). PMID 23741413.
^ Bousquet P (2002). „I1 imidazoline receptors: From the pharmacological basis to the therapeutic application” (pdf). Journal für Hypertonie. 6 (4): 6—9.
^ Jiang SX, Zheng RY, Zeng JQ, Li XL, Han Z, Hou ST (март 2010). „Reversible inhibition of intracellular calcium influx through NMDA receptors by imidazoline I(2) receptor antagonists”. Eur. J. Pharmacol. 629 (1–3): 12—9. PMID 19958763. doi:10.1016/j.ejphar.2009.11.063.

Spoljašnje veze уреди

Imidazoline+Receptors на US National Library of Medicine Medical Subject Headings (MeSH)
imidazoline receptor 2 на US National Library of Medicine Medical Subject Headings (MeSH)
imidazoline I1 receptors на US National Library of Medicine Medical Subject Headings (MeSH)

[pmid16529547-1] а ^б Head GA, Mayorov DN (јануар 2006). „Imidazoline receptors, novel agents and therapeutic potential”. Cardiovasc Hematol Agents Med Chem. 4 (1): 17—32. PMID 16529547. doi:10.2174/187152506775268758. Архивирано из оригинала 14. 4. 2013. г.

[PMID1327589-2] Hamilton CA, Yakubu MA, Howie CA, Reid JL (1992). „Do Centrally-Acting Antihypertensive Drugs Act at Non-Adrenergic as well as Alpha-2 Adrenoceptor Sites?”. Clinical and Experimental Hypertension Part A Theory and Practice. 14 (5): 815—835. PMID 1327589. doi:10.3109/10641969209036221.

[PMID1939285-3] Hamilton CA, Yakubu MA, Jardine E, Reid JL (1991). „Imidazole binding sites in rabbit kidney and forebrain membranes”. J Auton Pharmacol. 11 (5): 277—83. PMID 1939285. doi:10.1111/j.1474-8673.1991.tb00325.x.

[Regunathan-4] Regunathan, S; Reis, D J (април 1996). „Imidazoline Receptors and Their Endogenous Ligands”. Annual Review of Pharmacology and Toxicology. 36 (1): 511—544. PMID 8725400. doi:10.1146/annurev.pa.36.040196.002455.

[Kawamura-5] Kawamura, Kazunori; Shimoda, Yoko; Kumata, Katsushi; Fujinaga, Masayuki; Yui, Joji; Yamasaki, Tomoteru; Xie, Lin; Hatori, Akiko; Wakizaka, Hidekatsu; Kurihara, Yusuke; Ogawa, Masanao; Nengaki, Nobuki; Zhang, Ming-Rong (април 2015). „In vivo evaluation of a new 18F-labeled PET ligand, [18F]FEBU, for the imaging of I2-imidazoline receptors”. Nuclear Medicine and Biology. 42 (4): 406—412. PMID 25583220. doi:10.1016/j.nucmedbio.2014.12.014.

[Garcia-Sevilla-6] GARCIA-SEVILLA, JESUS A.; ESCRIBA, PABLO V.; GUIMON, JOSE (јун 1999). „Imidazoline Receptors and Human Brain Disorders”. Annals of the New York Academy of Sciences. 881 (1 IMIDAZOLINE R): 392—409. Bibcode:1999NYASA.881..392G. PMID 10415944. S2CID 10081479. doi:10.1111/j.1749-6632.1999.tb09388.x.

[Head-7] Head, G.; Mayorov, D. (1. 1. 2006). „Imidazoline Receptors, Novel Agents and Therapeutic Potential”. Cardiovascular & Hematological Agents in Medicinal Chemistry. 4 (1): 17—32. PMID 16529547. doi:10.2174/187152506775268758.

[pmid10415895-8] а ^б Ernsberger P (јун 1999). „The I1-imidazoline receptor and its cellular signaling pathways”. Ann. N. Y. Acad. Sci. 881 (1): 35—53. PMID 10415895. doi:10.1111/j.1749-6632.1999.tb09339.x. Архивирано из оригинала 2009-01-08. г. Приступљено 2014-06-30.

[pmid9374795-9] Reis DJ, Piletz JE (новембар 1997). „The imidazoline receptor in control of blood pressure by clonidine and allied drugs” (pdf). Am. J. Physiol. 273 (5 Pt 2): R1569—71. PMID 9374795.

[10] Han, Z; et al. „Fast, non-competitive and reversible inhibition of NMDA-activated currents by 2-BFI confers neuroprotection.”. PLoS One (2014). PMID 23741413.

[Bousquet_2002-11] Bousquet P (2002). „I1 imidazoline receptors: From the pharmacological basis to the therapeutic application” (pdf). Journal für Hypertonie. 6 (4): 6—9.

[pmid19958763-12] Jiang SX, Zheng RY, Zeng JQ, Li XL, Han Z, Hou ST (март 2010). „Reversible inhibition of intracellular calcium influx through NMDA receptors by imidazoline I(2) receptor antagonists”. Eur. J. Pharmacol. 629 (1–3): 12—9. PMID 19958763. doi:10.1016/j.ejphar.2009.11.063.

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