Regulation of vascular reactivity by established and emerging GPCRs

被引:68
作者
Maguire, JJ [1 ]
Davenport, AP [1 ]
机构
[1] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Ctr Clin Invest, Cambridge CB2 2QQ, England
关键词
D O I
10.1016/j.tips.2005.07.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The vascular system is rich in G-protein-coupled receptors (GPCRs), particularly Class 1 GPCRs, which are activated by an eclectic range of chemical entities including peptides. These chemical messengers can function in blood vessels as directly acting vasoconstrictors, directly acting vasodilators or indirectly acting vasodilators. During the past ten years >50 receptors previously designated as 'orphan receptors' have been paired with their cognate ligands. New transmitter systems are emerging with some displaying potent activity in the vascular system, including the vasoconstrictors apelin, motilin, neuromedin U, sphingosine-1-phosphate and urotensin-II, and the vasodilators ghrelin and nociceptin. All Class 2 GPCRs are activated by peptides. Those displaying Vasoactivity all function as directly acting vasodilators and include adrenomedullin and the emerging urocortin transmitters. Hypertension can persist despite treatment with combinations of blood-pressure-lowering drugs. Thus, it is likely that further as yet undiscovered transmitter systems will provide new targets for novel therapies or diagnosis.
引用
收藏
页码:448 / 454
页数:7
相关论文
共 70 条
[61]   ORPHANIN-FQ - A NEUROPEPTIDE THAT ACTIVATES AN OPIOID-LIKE G-PROTEIN-COUPLED RECEPTOR [J].
REINSCHEID, RK ;
NOTHACKER, HP ;
BOURSON, A ;
ARDATI, A ;
HENNINGSEN, RA ;
BUNZOW, JR ;
GRANDY, DK ;
LANGEN, H ;
MONSMA, FJ ;
CIVELLI, O .
SCIENCE, 1995, 270 (5237) :792-794
[62]   Urocortin II: A member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors [J].
Reyes, TM ;
Lewis, K ;
Perrin, MH ;
Kunitake, KS ;
Vaughan, J ;
Arias, CA ;
Hogenesch, JB ;
Gulyas, J ;
Rivier, J ;
Vale, WW ;
Sawchenko, PE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) :2843-2848
[63]   Maximizing serendipity: strategies for identifying ligands for orphan G-protein-coupled receptors [J].
Robas, N ;
O'Reilly, M ;
Katugampola, S ;
Fidock, M .
CURRENT OPINION IN PHARMACOLOGY, 2003, 3 (02) :121-126
[64]   Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor [J].
Tatemoto, K ;
Hosoya, M ;
Habata, Y ;
Fujii, R ;
Kakegawa, T ;
Zou, MX ;
Kawamata, Y ;
Fukusumi, S ;
Hinuma, S ;
Kitada, C ;
Kurokawa, T ;
Onda, H ;
Fujino, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 251 (02) :471-476
[65]  
Triggle Chris R., 2003, Journal of Smooth Muscle Research, V39, P249, DOI 10.1540/jsmr.39.249
[66]   CRF2 receptors are highly expressed in the human cardiovascular system and their cognate ligands urocortins 2 and 3 are potent vasodilators [J].
Wiley, KE ;
Davenport, AP .
BRITISH JOURNAL OF PHARMACOLOGY, 2004, 143 (04) :508-514
[67]   Comparison of vasodilators in human internal mammary artery: ghrelin is a potent physiological antagonist of endothelin-1 [J].
Wiley, KE ;
Davenport, AP .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 136 (08) :1146-1152
[68]   The identification of ligands at orphan G-protein coupled receptors [J].
Wise, A ;
Jupe, SC ;
Rees, S .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2004, 44 :43-66
[69]   Vasopeptidase inhibitors: will they have a role in clinical practice? [J].
Worthley, MI ;
Corti, R ;
Worthley, SG .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2004, 57 (01) :27-36
[70]   The relaxant effect of nociceptin on porcine coronary arterial ring segments [J].
Xu, PH ;
Chang, M ;
Cheng, LX ;
Cheng, Q ;
Yan, X ;
Wang, R .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 2004, 82 (11) :993-999