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

Access this Article

Search this Article

Author(s)

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 
Page Top