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      Direct coupling through gap junctions is not involved in urethral neurotransmission.

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          Abstract

          Interstitial cells of Cajal (ICC) are believed to participate in urethral neurotransmission and it was proposed that direct coupling of ICC and smooth muscle cells (SMC) through gap junctions (GJ) is involved, although this still remains unclear. Hence, we investigated the distribution of different connexins (Cx 43, Cx40, and Cx37) in the sheep and rat urethra, as well as their possible role in neurotransmission. Conventional PCR confirmed that three Cxs are expressed in the urethra. Moreover, both Cx43 and Cx37-immunoreactivity (-ir) were present in SMC, ICC, and the urothelium, although Cx37-ir was significantly weaker and Cx40-ir was limited to the endothelium. While these results indicate that GJ intercellular communication could occur between SMC and ICC, neither the contractile (noradrenergic) nor the relaxant (nitrergic) responses of the rat and sheep urethra to electrical field stimulation were significantly modified by two different GJ inhibitors: 18α-glycyrrhetinic acid and a cocktail of Cx mimetic peptides ((Cx43)Gap 26, (Cx37, Cx43)Gap 27, and (Cx40)Gap 27). By contrast, contractions induced by high K(+) were effectively reduced by both blockers, evidence that they effectively inhibit intercellular communication. These results indicate that GJ are not implicated in urethral neurotransmission, although the question of whether ICC modulate neurotransmission through some other mechanism remains to be determined.

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          Author and article information

          Journal
          Am. J. Physiol. Renal Physiol.
          American journal of physiology. Renal physiology
          1522-1466
          1522-1466
          Apr 2011
          : 300
          : 4
          Affiliations
          [1 ] Department of Physiology, Veterinary Faculty, Complutense University, Madrid, Spain.
          Article
          ajprenal.00641.2010
          10.1152/ajprenal.00641.2010
          21248015
          45e640d2-8f69-45f0-8850-547c7d48a9b5

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