title: Gq-linked NK(2) receptors mediate neurally induced contraction of human sigmoid circular smooth muscle.
abstract: OBJECTIVE
  Because tachykinins have been identified as neurotransmitters in the guinea pig colon and human ileum, we examined a possible role of tachykinin receptors and neurokinin (NK) A in neurally induced contraction of human sigmoid colon circular muscle.
  
  
  METHODS
  Muscle strips were stimulated electrically for 10 seconds. Single cells were isolated by enzymatic digestion and permeabilized by saponin. [(35)S]GTPgammaS binding was assayed with or without NKA for 5 minutes. Intracellular Ca(2+) was measured using Fura 2.
  
  
  RESULTS
  In the presence of 100 micromol/L L-NNA, 100 micromol/L atropine did not affect electrical field stimulation (EFS)-induced contraction. A peptide NK(2)-receptor antagonist (NK-2ra) but not an NK(1) antagonist FK888 (1 micromol/L) eliminated EFS-induced contraction. NKA-induced contraction in muscle strips and single cells was virtually abolished by NK-2ra, but not by FK888. In permeabilized cells, contraction was blocked by Gq-protein antibodies, but not by other G-protein antibodies, suggesting that NKA activates Gq, which was confirmed by a [(35)S]GTPgammaS binding assay. NKA-induced contraction and increase in cytosolic Ca(2+) were abolished by depletion of intracellular Ca(2+) stores.
  
  
  CONCLUSIONS
  Tachykinins may be the main excitatory neurotransmitters in human sigmoid circular muscle. NKA activates Gq-linked NK(2) receptors, which cause Ca(2+) release, followed by contraction.
authors.affiliation: Department of Medicine, Rhode Island Hospital, and Brown University School of Medicine, Providence, Rhode Island, USA.
authors.forename: W
authors.initials: W
authors.lastname: Cao
authors.forename: V E
authors.initials: VE
authors.lastname: Pricolo
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Behar
authors.forename: P
authors.initials: P
authors.lastname: Biancani
authors.forename: M T
authors.initials: MT
authors.lastname: Kirber
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000502:physiology; D003106:Colon / Q000166:cytology / Q000294:innervation / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D009424:Nervous System Physiological Phenomena; D015288:Neurokinin A / Q000494:pharmacology; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D004151:Dipeptides; D007211:Indoles; D018041:Receptors, Neurokinin-2; C078949:FK 888; D015288:Neurokinin A; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium