title: Evidence for signaling via gap junctions from smooth muscle to endothelial cells in rat mesenteric arteries: possible implication of a second messenger.
abstract: We investigated heterocellular communication in rat mesenteric arterial strips at the cellular level using confocal microscopy. To visualize Ca(2+) changes in different cell populations, smooth muscle cells (SMCs) were loaded with Fluo-4 and endothelial cells (ECs) with Fura red. SMC contraction was stimulated using high K(+) solution and Phenylephrine. Depending on vasoconstrictor concentration, intracellular Ca(2+) concentration ([Ca(2+)](i)) increased in a subpopulation of ECs 5-11s after a [Ca(2+)](i) rise was observed in adjacent SMCs. This time interval suggests chemical coupling between SMCs and ECs via gap junctions. As potential chemical mediators we investigated Ca(2+) or inositol 1,4,5-trisphosphate (IP(3)). First, phospholipase C inhibitor U-73122 was added to prevent IP(3) production in response to the [Ca(2+)](i) increase in SMCs. In high K(+) solution, all SMCs presented global and synchronous [Ca(2+)](i) increase, but no [Ca(2+)](i) variations were detected in ECs. Second, 2-aminoethoxydiphenylborate, an inhibitor of IP(3)-induced Ca(2+) release, reduced the number of flashing ECs by 75+/-3% (n = 6). The number of flashing ECs was similarly reduced by adding the gap junction uncoupler palmitoleic acid. Thus, our results suggest a heterocellular communication through gap junctions from SMCs to ECs by diffusion, probably of IP(3).
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratory of Cell Biophysics (LCB), CH-1015 Lausanne, Switzerland. mathieu.lamboley@epfl.ch
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lamboley
authors.forename: Philippe
authors.initials: P
authors.lastname: Pittet
authors.forename: Michèle
authors.initials: M
authors.lastname: Koenigsberger
authors.forename: Roger
authors.initials: R
authors.lastname: Sauser
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bény
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Meister
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D016257:Fura-2 / Q000031:analogs & derivatives; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D001896:Boron Compounds; D004791:Enzyme Inhibitors; D004963:Estrenes; D005229:Fatty Acids, Monounsaturated; D011760:Pyrrolidinones; C049925:fura-2-am; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D010656:Phenylephrine; C008757:palmitoleic acid; D015544:Inositol 1,4,5-Trisphosphate; C109986:2-aminoethoxydiphenyl borate; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2