Connexin-made channels as pharmacological targets

被引:41
作者
Hervé, JC
Sarrouilhe, D
机构
[1] Univ Poitiers, CNRS, UMR 6187, Equipe Interact & Commun Cellulaires,Fac Sci Fund, F-86022 Poitiers, France
[2] Univ Poitiers, Fac Med & Pharm, Lab Physiol Humaine, F-86022 Poitiers, France
关键词
Gap junctions; connexin; junctional uncoipling;
D O I
10.2174/1381612054021060
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Gap junctions are clusters of intercellular channels that provide morphological support for direct diffusion of ions and low-molecular-weight molecules between adjacent coupled cells. Each gap junction channel is made by docking of two hemichannels or connexons, each formed by assembly of six proteins (connexins). 21 members of the connexin gene family are likely to be expressed in the human genome. These ubiquitous gated channels, allowing rapid intercellular communication and synchronisation of coupled cell activities, play critical roles in many signalling processes, including co-ordinated cardiac and smooth muscle contractions, neuronal excitability, neurotransmitter release, insulin secretion, epithelial electrolyte transport, etc. Mutational alterations in the connexin genes are associated with the occurrence of multiple pathologies, such as peripheral neuropathies, cardiovascular diseases, dermatological diseases, hereditary deafness and cataract. But the neuro- and cardioprotective effects of blocking agents of junctional channels show that closure of these channels may also be beneficial in certain pathological situations. Consequently, modulation of gap junctional intercellular communication is a potential pharmacological target. In contrast to most other membrane channels, no natural toxin or specific inhibitor of junctional channels has been identified yet and most uncoupling agents generally also affect other ionic channels and receptors. Future research, based for example on the recent developments in genetics, may clarify gap junction physiology. This will in turn provide promising perspectives for the development of targeted drugs.
引用
收藏
页码:1941 / 1958
页数:18
相关论文
共 219 条
[1]   Cell-to-cell communication and expression of gap junctional proteins in human diabetic and nondiabetic skin fibroblasts -: Effects of basic fibroblast growth factor [J].
Abdullah, KM ;
Luthra, G ;
Bilski, JJ ;
Abdullah, SA ;
Reynolds, LP ;
Redmer, DA ;
Grazul-Bilska, AT .
ENDOCRINE, 1999, 10 (01) :35-41
[2]   Assembly of gap junction channels - Mechanism, effects of calmodulin antagonists and identification of connexin oligomerization determinants [J].
Ahmad, S ;
Martin, PEM ;
Evans, WH .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (16) :4544-4552
[3]   Rapid and reversible effects of activity on acetylcholine receptor density at the neuromuscular junction in vivo [J].
Akaaboune, M ;
Culican, SM ;
Turney, SG ;
Lichtman, JW .
SCIENCE, 1999, 286 (5439) :503-507
[4]  
AONUMA S, 1980, CHEM PHARM BULL, V28, P3340
[5]   STUDIES ON HEART .21. AMINO-ACID-SEQUENCE OF ANTIARRHYTHMIC PEPTIDE (AAP) ISOLATED FROM ATRIA [J].
AONUMA, S ;
KOHAMA, Y ;
MAKINO, T ;
FUJISAWA, Y .
JOURNAL OF PHARMACOBIO-DYNAMICS, 1982, 5 (01) :40-48
[6]   Inhibition of endothelial cell migration, intercellular communication, and vascular tube formation by thromboxane A2 [J].
Ashton, AW ;
Yokota, R ;
John, G ;
Zhao, SM ;
Suadicani, SO ;
Spray, DC ;
Ware, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (50) :35562-35570
[7]   Effect of antipeptide antibodies directed against three domains of connexin43 on the gap junctional permeability of cultured heart cells [J].
Bastide, B ;
JarryGuichard, T ;
Briand, JP ;
Deleze, J ;
Gros, D .
JOURNAL OF MEMBRANE BIOLOGY, 1996, 150 (03) :243-253
[8]   RAPID ONSET AND CALCIUM INDEPENDENCE OF THE GAP JUNCTION UNCOUPLING INDUCED BY HEPTANOL IN CULTURED HEART-CELLS [J].
BASTIDE, B ;
HERVE, JC ;
CRONIER, L ;
DELEZE, J .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1995, 429 (03) :386-393
[9]  
BECKER DL, 1995, J CELL SCI, V108, P1455
[10]   A method to determine the relative cAMP permeability of connexin channels [J].
Bedner, P ;
Niessen, H ;
Odermatt, B ;
Willecke, K ;
Harz, H .
EXPERIMENTAL CELL RESEARCH, 2003, 291 (01) :25-35