Mouse vas deferens preparation

Tamura T, Ogawa J, Taniguchi T, Waki I (1990) Preferential action of eptazocine, a novel analgesic, with opioid receptors in isolated guinea pig ileum and mouse vas deferens preparations. Folia Pharmacol Japon 95 41 16... 

Campbell, C., Jolly, N., Bom, A., and Cottney, J. (2003) The actions of six cannabinoid agonists in mouse vas deferens preparations nnder two different stimulation conditions. Proc. Br. Pharmacol. Soc. at http //www.pa2online.org/ Volllssue3abst044P.html. 

Pertwee RGS, L. A. Elrick DB, Mechoulam R, Corbett AD. Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and the myenteric plexus preparation of guinea-pig small intestine. Br J Pharmacol 1992 105 980-984. 

The opioid agonistic activities of ( )-TAN-67, its derivatives 71d and 71f, and DPDPE were evaluated on electrically stimulated guinea-pig ileum (GPI) and mouse vas deferens (MVD) preparations (Table 4) [34,36]. It is known that ix and k opioid receptors are predominantly expressed in GPI and the 8 receptor is predominantly expressed in MVD [37,38]. The IC50 value is the index of agonistic activity—the smaller its value, the more potent the agonistic... 

Cannabinoid and endocannabinoid-induced synaptic depression is observed in both the peripheral nervous system and the CNS. Indeed, A9-THC inhibition of transmitter release was first demonstrated in mouse vas deferens (Graham et al. 1974), and further evidence for presynaptic inhibition has been obtained using this preparation (Ishac et al. 1996 Pertwee and Fernando 1996) and in the myenteric plexus (Coutts and Pertwee 1997 Kulkami-Narla and Brown 2000). In addition, anandamide was first characterized as an EC based on its actions in the mouse vas deferens (Devane et al. 1992). Subsequently, CB1 receptor-mediated inhibition of release of several neurotransmitters has been documented in various regions of the PNS (see Szabo and Schlicker 2005 for review). Cannabinoids also inhibit neural effects on contraction in the ileum (Croci et al. 1998 Lopez-Redondo et al. 1997), although it is not clear that this is effect involves direct inhibition of neurotransmitter release (Croci et al. 1998). The CB1 receptor has been localized to enteric neurons, and thus the effect on ileum certainly involves actions on these presynaptic neurons. In addition, anandamide produces ileal relaxation via a non-CBl, non-CB2-mediated mechanism (Mang et al. 2001). 

There are two major groups of synthetic compounds which have cannabin-oid activity, but which differ chemically from the tricyclic THC-like canna-binoids the bicyclic cannabinoids, exemplified by compound CP55940 (23), and the (aminoalkyl)indoles exemplified by pravadoline (24a). A detailed SAR analysis of these groups of compounds is beyond the scope of this review. The bicyclic cannabinoids and derivatives have been reviewed previously [105] recent publications deal mainly with related tricyclic non-classical cannabinoids [106] and with the (aminoalkyl)indoles [92, 107]. It is of interest to note that while the bicyclic cannabinoids were originally prepared as simplified cannabinoids, the cannabinoid-type activity of the (ami-noalkyl)indoles was discovered by serendipity. These compounds were synthesized in a project aimed at the discovery of novel nonsteroidal anti-inflammatory agents presumably based on the indomethacin structure. However, while they did not possess anti-inflammatory properties, they were found to be antinociceptive, and to inhibit the electrically evoked contractions in a mouse vas deferens muscle preparation. This led to binding experi-... 

Results from previous experiments, in which we compared the inhibitory effects of the 1,1-dimethylheptyl homologs of (+) and (-)-ll-hydroxy-delta-8-tetrahydrocannabinol on the electrically-evoked twitch response of the mouse vas deferens, indicate that this preparation is suitable as a model for investigating the mode(s) of action of psychotropic cannabinoids. R. G. Pertwee, L. A. Stevenson, D. B. Elrick, R. Mechoulam, A. D. Corbett, Brit. J. Pharmacol. 105, 980 (1992). Anandamide produced a concentration-dependent inhibition of the twitch response (FIG. 2). The inhibition was not reversed by naloxone (300 nM). The levels of inhibition are comparable to those of binding to the receptor. 

A second antagonist, AM 630 (24b), a novel aminoalkylindole, was found to attenuate the ability of some cannabinoids to inhibit electrically-evoked twitches of the mouse isolated vas deferens [114]. AM 630 was a more potent antagonist of d9-THC than of anandamide (Kd of 14.0 and 278.8 nM, respectively). It was suggested that the receptors for which AM 630 has the highest activity may not be CB, cannabinoid receptors. This is supported by the observation that AM 630 is actually a cannabinoid agonist in the myenteric plexus - muscle preparation [115]. Yamada et al. [116] showed that isothiocyanate derivatives of pravadoline can serve as potential electrophilic affinity ligands for CB],... 

One in vitro preparation that has been widely used as a bioassay for characterizing the pharmacological properties of CBi receptor agonists is the mouse isolated vas deferens. This bioassay rehes on the presence in this tissue of native neuronal CBi receptors and on the ability of CBi agonists to interact with these receptors to produce a concentration-related decrease in the amplitude of... 

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