The obligatory link: role of gap junctional communication in endothelium-dependent smooth muscle hyperpolarization. 2004

Tudor M Griffith, and Andrew T Chaytor, and David H Edwards
Department of Diagnostic Radiology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK. griffith@cardiff.ac.uk

Although an endothelium-derived hyperpolarizing factor (EDHF) has often been hypothesized to underpin vascular relaxations that are independent of nitric oxide (NO) and prostanoids, bioassay techniques have failed to confirm the existence of a freely transferable EDHF in a consistent fashion. Indeed, observations that inhibitors of direct cell-cell coupling such as connexin-mimetic peptides (e.g. Gap 26 and 27) and glycyrrhetinic acid derivatives attenuate "EDHF-type" smooth muscle hyperpolarizations and relaxations suggest that an electrotonic spread of endothelial hyperpolarization via myoendothelial and homocellular smooth muscle gap junctions plays an obligatory role in such responses. The endothelial hyperpolarization that initiates relaxation results from the opening of K(Ca) channels and is sustained by capacitative Ca(2+) entry triggered by the depletion of intracellular Ca(2+) stores in the endoplasmic reticulum. EDHF-type relaxations are also associated with a prostanoid-independent synthesis of cAMP that increases the conductance of gap junction channels and enhances the transmission of endothelial hyperpolarization through the vascular wall in a permissive fashion. This review will discuss the roles of these interacting signalling pathways in the mediation of the EDHF phenomenon.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D002450 Cell Communication Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. Cell Interaction,Cell-to-Cell Interaction,Cell Communications,Cell Interactions,Cell to Cell Interaction,Cell-to-Cell Interactions,Communication, Cell,Communications, Cell,Interaction, Cell,Interaction, Cell-to-Cell,Interactions, Cell,Interactions, Cell-to-Cell
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001685 Biological Factors Endogenously synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS. Biologic Factors,Biological Factor,Factor, Biologic,Factor, Biological,Factors, Biological,Biologic Factor,Factors, Biologic
D017629 Gap Junctions Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of CONNEXINS, the family of proteins which form the junctions. Gap Junction,Junction, Gap,Junctions, Gap

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