Evidence that cannabinoid-induced inhibition of electrically evoked contractions of the myenteric plexus--longitudinal muscle preparation of guinea-pig small intestine can be modulated by Ca2+ and cAMP

Can J Physiol Pharmacol. 1998 Mar;76(3):340-6.

Abstract

Cannabinoid receptor agonists inhibit electrically evoked isometric contractions of the myenteric plexus--longitudinal muscle preparation of the guinea-pig small intestine (MPLM), probably by reducing release of acetylcholine (ACh) through the activation of prejunctional CB1 receptors. As CB1 receptors are thought to be negatively coupled through Gi/o proteins to both N-type Ca2+ channels and adenylate cyclase, we have now further investigated the involvement of CB1 receptors by monitoring the effects of forskolin, 8-bromo-cAMP, 3-isobutyl-1-methylxanthine (IBMX), and extracellular Ca2+ on the ability of the cannabinoid agonist, (+)-WIN 55212 to inhibit electrically evoked contractions of the MPLM (0.1 Hz, 0.5 ms, and 110% maximal voltage). Some experiments were performed with normorphine instead of (+)-WIN 55212. At 10(-7) M, forskolin, 8-bromo-cAMP, and IBMX were found to reduce significantly the maximum inhibitory response to (+)-WIN 55212 by 49.4, 48.4, and 40.2%, respectively, without affecting control contractions or responses to exogenous ACh. Low external Ca2+ (0.64 mM) significantly increased the maximum response to (+)-WIN 55212 and shifted the curve slightly leftwards, whereas high external Ca2+ (5.08 mM) reduced the maximum response by 27.2%. The concentration-response curve to normorphine, which also reduces evoked contractions of this preparation as a result of a presynaptic inhibition of ACh release via opioid mu receptors, was affected similarly. These results support the hypothesis that cannabinoid-induced inhibition in the MPLM is mediated by CB1 receptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenylate Cyclase Toxin
  • Animals
  • Benzoxazines
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Cannabinoids / pharmacology*
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Guinea Pigs
  • Intestine, Small / drug effects*
  • Intestine, Small / physiology
  • Male
  • Morphine Derivatives / pharmacology
  • Morpholines / pharmacology
  • Muscle Contraction / drug effects*
  • Myenteric Plexus / drug effects*
  • Myenteric Plexus / physiology
  • Naphthalenes / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology
  • Receptors, Cannabinoid
  • Receptors, Drug / physiology*
  • Receptors, Opioid, mu / agonists
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Adenylate Cyclase Toxin
  • Benzoxazines
  • Calcium Channel Blockers
  • Cannabinoids
  • Morphine Derivatives
  • Morpholines
  • Naphthalenes
  • Phosphodiesterase Inhibitors
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Receptors, Opioid, mu
  • Virulence Factors, Bordetella
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Win 55212-2
  • Cyclic AMP
  • Calcium
  • 1-Methyl-3-isobutylxanthine
  • normorphine