Muscarinic Receptors Controlling the Carbachol-Activated Nonselective Cationic Current in Guinea Pig Gastric Smooth Muscle Cells

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Abstract

Muscarinic receptor subtypes controlling the nonselective cationic current in response to carbachol(I<SUB>CCh</SUB>)were studied in circular smooth muscle cells of the guinea pig gastric antrum using putative muscarinic agonists and antagonists.Both oxotremorine-M(an M<SUB>2</SUB>-selective agonist)and CCh dose-dependently activated the cationic current with EC<SUB>50</SUB> values of 0.21±0.01μm and 0.97±0.06μM, respectively.In contrast, pilocarpine and McN-A 343(an M<SUB>1</SUB>-selective and a putative M<SUB>4</SUB> agonist)were weak partial agonists.In response to 10μM CCh, 4-DAMP, methoctramine and pirenzepine dose-dependently inhibited I<SUB>CCh</SUB> and had IC<SUB>50</SUB> values of 1.91±0.2nM, 0.46±0.07μM and 8.33±0.4μM, respectively.4-DAMP, methoctramine and pirenzepine shifted the concentration-response curves of I<SUB>CCh</SUB> to the right without significantly reducing the maximal current.Values of the apparent dissociation constant pA<SUB>2</SUB> obtained from Schild plot analysis were 9.24, 7.72 and 6.62 for 4-DAMP, methoctramine and pirenzepine, respectively.Also, pertussis toxin completely blocked I<SUB>CCh</SUB> generation.These results suggest that the M<SUB>2</SUB>-subtype plays a crucial role in the activation of the I<SUB>CCh</SUB>, and a block of the M<SUB>3</SUB>-subtype reduces the sensitivity of the M<SUB>2</SUB>-mediated response with no significant reduction of maximum response.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 82(4), 331-337, 2000-04-01

    The Japanese Pharmacological Society

References:  21

Cited by:  4

Codes

  • NII Article ID (NAID)
    10008183964
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    5362808
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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