Protease-activated receptors mediate apamin-sensitive relaxation of mouse and guinea pig gastrointestinal smooth muscle

Gastroenterology. 1999 Mar;116(3):586-92. doi: 10.1016/s0016-5085(99)70180-0.


Background & aims: Protease-activated receptor (PAR)-1 and PAR-2 are expressed on gastrointestinal smooth muscle, but knowledge of their functionality is limited. The aim of this study was to determine if PAR-1 and PAR-2 mediate gastrointestinal smooth muscle relaxation and to clarify the underlying mechanisms.

Methods: Responses to PAR activation using the serine proteases thrombin and trypsin and the peptide agonists for PAR-1 and PAR-2, SFLLRN-NH2 and SLIGRL-NH2, respectively, were investigated in submaximally contracted longitudinal strips of mouse gastric fundus and guinea pig taenia coli.

Results: In mouse gastric fundus, both thrombin and trypsin caused relaxations followed by contractions. SFLLRN-NH2 and SLIGRL-NH2 caused similar biphasic responses, the relaxation components of which were eliminated by apamin or ryanodine. For SFLLRN-NH2, apamin and ryanodine revealed contractions. Nifedipine inhibited both relaxations and contractions to each peptide. In guinea-pig taenia coli, thrombin but not trypsin caused relaxation, whereas SFLLRN-NH2 and SLIGRL-NH2 caused concentration-dependent relaxations that were eliminated by apamin but were unaffected by ryanodine.

Conclusions: The mouse gastric fundus and guinea pig taenia coli contain functional PAR-1 and PAR-2 that mediate relaxations via ryanodine-sensitive and -insensitive activation of small-conductance, Ca2+-activated K+ channels. We propose that smooth muscle PARs act as sensors for inflammatory signals in gut and respond by inhibiting gut motility during peritoneal infections or tissue damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Apamin / pharmacology*
  • Calcium Channel Blockers / pharmacology
  • Colon / drug effects
  • Colon / physiology*
  • Gastric Fundus
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Nitroarginine / pharmacology
  • Oligopeptides / pharmacology
  • Peptide Fragments / pharmacology
  • Receptor, PAR-1
  • Receptor, PAR-2
  • Receptors, Thrombin / drug effects
  • Receptors, Thrombin / physiology*
  • Stomach / drug effects
  • Stomach / physiology*
  • Tetrodotoxin / pharmacology
  • Thrombin / pharmacology


  • Calcium Channel Blockers
  • Oligopeptides
  • Peptide Fragments
  • Receptor, PAR-1
  • Receptor, PAR-2
  • Receptors, Thrombin
  • seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide
  • thrombin receptor peptide (42-47)
  • Nitroarginine
  • Apamin
  • Tetrodotoxin
  • Thrombin
  • Acetylcholine