Mouse vas deferens

Basbaum, CB and Heuser, JE (1979) Morphological studies of stimulated adrenergic axon varicosities in the mouse vas deferens. J. Cell Biol. 80 310-325. 

Following on from this they demonstrated that the aminoethyl side chain could also be replaced (see Table 6.22) [180], the most potent ligands bearing a naphthoyl moiety. In particular, the piperidinyl analogue (258) was found to have a high affinity in the binding assay and potency in the mouse vas deferens assay. 

Mouse vas deferens (MVD) seems to express CB1 and at least one CB2-like cannabinoid receptor type, as is demonstrated by the presence of CB1 and CB2-like mRNA as well as by data collected from experiments with cannabinoid receptor selective agonists and antagonists (Pertwee, 1999). Furthermore, evidence indicates that a CBl-like receptor exists in vascular endothelium, which upon activation produces significant hypotension (Wagner, 1999). This receptor differs from CB1 in its pharmacological response to some well-characterized cannabimimetics. 

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. 

Brockstedt E et al. Luteinizing hormone induces mouse vas deferens protein expression in the murine ovary. Endocrinology 2000 141 2574-2581. 

Pailhoux EA, Martinez A, Veyssiere GM, Jean CG. Androgen-dependent protein from mouse vas deferens cDNA cloning and protein homology with the aldo-keto reductase superfamily. J Biol Chem 1990 265 19932-19936. 

These peptides were characterized in vitro and found to be powerful opioid agonists in the mouse vas deferens (MVD) and guinea pig ileum (GPI) assay. In vivo (rat tail-flick) they are only active when administered directly to the brain - a general limitation of simple linear peptides consisting of natural L-amino acids - but with less potency and shorter duration of action than morphine (Casy and Parfitt, 1986). 

NTI shows subnanomolar affinity for the 5 opioid receptor along with a very potent antagonistic activity in the mouse vas deferens... 

Fang, L., Knapp, R.J., Horvath, R., Matsunaga, T. O., Haaseth, R. C., Hruby, V. J., Porreca, F., Yamamura, H. I. Characterization of fl-IJnaltrindole binding to delta opioid receptors in mouse brain and mouse vas deferens Evidence for delta opioid receptor heterogeneity, J. Pharmacol. Exp. Ther. 1994, 268, 836-846. 

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... 

Y receptors can couple to voltage-dependent K+ channels (step 3 in Figure 3). This may hold true for the neuropeptide Y receptor involved in inhibition of ATP release in the mouse vas deferens (Stjame et al. 1989). For three presynaptic neuropeptide... 

Allen JM, Adrian TE, Tatemoto K et al (1982) Two novel related peptides, neuropeptide Y (NPY) and peptide YY (PYY) inhibit the contraction of the electrically stimulated mouse vas deferens. Neuropeptides 3 71-7... 

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). 

ENKEPHALIN IS MORE POTENT THAN MORPHINE IN MOUSE VAS DEFERENS... 

This hypothesis of delta receptors in the mouse vas deferens was later further substantiated by the observation of the lack of cross-tolerance between a stable enkephalin analog [D-Ala2, D-leu5]enkephalin (DADLE, see below) and sulphentanyl (a mu agonist) in this tissue after chronic administration in vivo [8]. 

In contrast to the mouse vas deferens, the guinea pig ileum contains predominately mu receptors and less kappa receptors, but no delta receptors. The function of mu and kappa receptors can be examined independently in the presence of a selective kappa antagonist (i.e., nor-BNI) and a mu antagonist (i.e., CTOP), respectively, similar to that described above for the mouse vas deferens [9]. The potency of mu and kappa agonists often exhibits higher potency in the guinea pig ileum than that obtained from the mouse vas deferens. 

TABLE 2 Inhibitory Potencies of Deltorphins and Some Analogues on Electrically Evoked Contractions of Mouse Vas Deferens (MVD) and Guinea Pig Ileum (GPI), and on the Specific Binding of 0.3 nM [3H]D-Ala-Deltorphin-I and of 0.5 nM [3H]DAGO at Delta and Mu Sites in Rat Brain Membranes... 

Further studies in mouse vas deferens indicated that DPI-3290 is also active at mu opioid receptors. The intrinsic activity of DPI-3290 at mu opioid receptors was determined in the presence of the highly selective delta opioid receptor antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH) (3 pM) and the selective kappa opioid receptor antagonist nor-BNI (15 nM). Under these conditions, DPI-3290 again caused concentration-dependent inhibition of muscle contraction with a corresponding IC50 value of 6.2 2.0 nM. Although far less potent at kappa opioid receptors in comparison to its intrinsic activity at mu... 

PENK), prodynorphin (PDYN), and pro-opiomelanocortin (POMC) [13-15]. PENK was originally discovered in bovine adrenal cortex and pig brain, where enkephalin biosynthesis was elucidated [13]. It contains one copy of Leu-enkephalin, four copies of Met-enkephalin, and one copy each of a Met-enkephalin C-terminal-extended heptapeptide and octapeptides, all flanked by basic dipeptides, where processing generally takes place. The primary identification of delta opioid receptors was a direct consequence of the discovery of these enkephalins [16]. These peptides were first examined for their potency at opioid receptors present in the guinea pig ileum and mouse vas deferens bioassays. The result of these studies shows that enkephalins are acting at a different receptor in the mouse vas deferens than the guinea pig ileum and this receptor for enkephalins was defined as the elimination of the delta opioid receptor [17]. 

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