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 G(i/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.
| Original language | English |
|---|---|
| Pages (from-to) | 340-346 |
| Number of pages | 7 |
| Journal | Canadian Journal of Physiology and Pharmacology |
| Volume | 76 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 1998 |
Keywords
- cannabinoid
- myenteric
- calcium
- cAMP
- normorphine
- MOUSE VAS-DEFERENS
- PERTUSSIS-TOXIN
- RECEPTOR
- RELEASE
- TRANSMISSION
- ANTAGONIST
- AGONIST
- PROTEIN
- BINDS
- CB1
Cite this
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. / Coutts, Angela Alice; Pertwee, Roger Guy.
In: Canadian Journal of Physiology and Pharmacology, Vol. 76, No. 3, 03.1998, p. 340-346.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence that cannabinoid-induced inhibition of electrically evoked contractions of the myenteric plexus
T2 - longitudinal muscle preparation of guinea-pig small intestine can be modulated by Ca2+ and camp
AU - Coutts, Angela Alice
AU - Pertwee, Roger Guy
PY - 1998/3
Y1 - 1998/3
N2 - 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 G(i/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.
AB - 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 G(i/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.
KW - cannabinoid
KW - myenteric
KW - calcium
KW - cAMP
KW - normorphine
KW - MOUSE VAS-DEFERENS
KW - PERTUSSIS-TOXIN
KW - RECEPTOR
KW - RELEASE
KW - TRANSMISSION
KW - ANTAGONIST
KW - AGONIST
KW - PROTEIN
KW - BINDS
KW - CB1
U2 - 10.1139/cjpp-76-3-340
DO - 10.1139/cjpp-76-3-340
M3 - Article
VL - 76
SP - 340
EP - 346
JO - Canadian Journal of Physiology and Pharmacology
JF - Canadian Journal of Physiology and Pharmacology
SN - 0008-4212
IS - 3
ER -