Vanilloid system

Convergence between Opioid, Cannabinoid, and Vanilloid Systems in Pain Pathways... 

The expression of TRPVl in the bladder is, however, not restricted to afferent nerves urothelium, detrusor muscle and fibroblasts also express TRPVl in the human bladder [140]. The implication of these findings for intravesical vanilloid therapy is unclear [141], but the increase in TRPVl immunoreactivity in the urothelium in patients with neurogenic detrusor overactivity (that occurs in concert with increased TRPVl in bladder af-ferents) is a very intriguing finding [142]. In the male urogenital system, TRPVl is also present in testicles, prostate and scrotal skin [143], and it was postulated that TRPVl ligands may be beneficial in the treatment of benign prostatic hyperplasia [144]. 

Epidermis is an interface between body and environment. The basic mechanism of the smart system of the epidermis has not been clarified yet, but epidermal ion dynamics in the epidermis plays an important role as a signaling system.47,49 As described earlier, a variety of receptors of neurotransmitters are found in the keratinocytes. Recently, the existence and function of vanilloid receptor subtype 1 (VR1, TRPV1) in epidermal keratinocytes has been demonstrated (Figure 10.2).50,51... 

Several neural receptors have been isolated recently within the epidermis of humans and mice. Many of these receptors, such as vanilloid receptor 1, are associated with ion dynamics in the peripheral nervous system.38 Since skin barrier function is also predicated on ion gradient stability,15,39 these receptors might be inducing transmission of itch related to barrier impairment. 

Benzisothiazole 1,1-dioxide is claimed as an antagonist of the vanilloid receptor with analgesic activity <2006W02006065646>. Isothiazolopyridine derivatives show analgesic activity as a result of stimulation of the serotoninergic system <2005FES961>. 

Mezey E, Toth ZE, Cortright DN, Arzubi MK, Krause JE, Elde R, Guo A, Blumberg PM, Szallasi A (2000) Distribution of mRNA for vanilloid receptor subtype 1 (VRl), and VRl-like immunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci USA 97 3655-3660... 

It is possible that the endocannabinoid system is taking part in thermoregulation, too. However, it is still questionable whether this effect occurs by the activation of cannabinoid receptors and/or vanilloid receptor, or by other mechanisms. 

Di Marzo V, Bisogno T, Melck D, Ross R, Brockie H, Stevenson L, Pertwee R, De Petrocellis L (1998) Interactions between synthetic vanilloids and the endogenous cannabinoids system. FEBS Lett 436 449-454... 

Cetirizine competitively antagonizes histamine at the Hi-receptor site and is indicated in the symptomatic relief of symptoms (e.g., nasal, nonnasal) associated with seasonal and perennial allergic rhinitis treatment of uncomplicated skin manifestations of chronic idiopathic urticaria. Histamine is a potent vasodilator, bronchial smooth-muscle constrictor, and stimnlant of nociceptive itch nerves. In addition to histamine, mnltiple chemical itch mediators can act as pruritogens on C-fibers, including neuropeptides, prostaglandins, serotonin, acetylcholine, and bradykinin. Furthermore, new receptor systems such as vanilloid, opioid, and canna-binoid receptors on cutaneous sensory nerve fibers that may modulate itch offer novel targets for antipruritic therapy. 

T. Hokfelt, J.M. Lundberg, Vanilloid (capsaicin) receptors in the rat distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment, Brain Res. 1995, 703, 175-183. 

Di Marzo, V, Bisogno, T., Melck, D., Ross, R, Brockie, H., Stevenson, E., Pertwee, R. G. and De Petrocellis, L. (1998a) Interactions between synthetic vanilloids and the endogenous cannabinoid system. FEES Lett. 436, 449 54. 

It clearly appears that if the endocannabinoid system really plays a role in the physiopathology of schizophrenia, the activation of CBj receptors does not seem to be a crucial point. Interestingly, CBi is not the sole CB receptor subtype expressed in the brain. Some studies using CB, KO mice supported the existence of G-protein-coupled non-CBj and non-CBj cannabinoid receptors, sensitive to endocannabinoids, synthetic agonists, and rimonabant (Di Marzo et al., 2000 Breivogel et al., 2001 Pride et al., 2003). In addition, anandamide has been found to activate both CB, and vanilloid VR, receptors (for review see Di Marzo et al., 2002). However, the localizations and functions of such types of receptors are unclear, and their putative role in schizophrenia remains to be demonstrated. Although cannabis use appears to be neither a sufficient nor a necessary cause for psychosis, the current status of research on cannabis-associated psychosis (Leweke et al., 2004) is inconclusive, and further research is needed to understand the mechanisms by which cannabis is associated with psychosis. 

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