Electrically evoked contractions

Later 2-AG was also found in the brain (Stella, 1997) and spleen (Di Marzo, 1998). It was shown to be released in a calcium-dependent manner, reaching concentrations 170 times higher than that of anandamide in the brain (Stella, 1997). Like the other endocannabinoids, 2-AG was shown to produce the typical tetrad of cannabimimetic behavioral effects and inhibit electrically evoked contractions of mouse MVD (Mechoulam, 1995a). 

Pertwee RG, Fernardo SR, Griffin G, Abadji Y, Makriyannis A. Effect of phenylmethylsulphonyl fluoride on the potency of anandamide as an inhibitor of electrically evoked contractions in two isolated tissue preparations. Eur J Pharmacol 1995b 272 73-78. 

Menkveld, G.J., Timmerman, H., 1990. Inhibition of electrically-evoked contractions of guinea-pig ileum preparations mediated by the histamine H3 receptor. Eur. J. Pharmacol. 186, 343-347. 

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... 

In the dog, electrically evoked contractions of the lower esophageal sphincter are inhibited by DPDPE, a response interpreted to indicate the involvement of delta opioid receptors [72]. On the other hand, DADLE increases lower esophageal sphincter pressure in the opossum. As the mu opioid agonists meperidine and buprenorphine both reduce sphincter pressure, the opposite effect of DADLE is probably mediated by delta opioid receptors [73],... 

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-... 

An assay that measures the ability of ligands to inhibit electrically evoked contractions of the mouse vas deferens. 

Cannabinoids also inhibit transmitter release from cholinergic autonomic neurons (Table 4). As an example, the bradycardia elicited by vagal nerve stimulation is depressed. Figure 5B shows that cannabinoids inhibit parasympathetic neuroeffector transmission in the heart. Electrically evoked contractions of the ileum and urinarybladder can also be inhibited by activation of CBi receptors (Table 4). 

Noradrenaline Rat Vas deferens Electrically evoked contraction Christopoulos etal. 2001... 

Noradrenaline, ATP Mouse Vas deferens Electrically evoked contraction Pertwee et al. 1992,2002... 

Acetylcholine, ATP Mouse Urinary bladder Electrically evoked contraction Pertwee and Fernando 1996... 

Acetylcholine Guinea-pig Ileum Electrically evoked contraction, acetylcholine Pertwee et al. 1992,1996b Lopez-... 

Acetylcholine Man Ileum Electrically evoked contraction Croci etal. 1998... 

Grundemar, L. Hakanson, R. (1990) Effects of various neuropeptide Y/peptide YY fragments on electrically-evoked contractions of the rat vas deferens. Br.J. Pharmacol. 100, 190-192. 

Histamine receptors have been classified into two major subtypes, H, and H2, on the basis of quantitative studies on isolated peripheral tissues. Histamine H,-receptors mediate the contractile actions of histamine on numerous visceral smooth muscles, most notably from the trachea, ileum and uterus of the guinea-pig [36-39]. These responses are antagonized by the classical -antihistamines [36-39] such as mepyramine (1) [36] and diphenhydramine (3) [40] (see Figure 2.1). Histamine also stimulates the secretion of acid by stomach, increases the rate of contraction of guinea-pig isolated atria and inhibits electrically evoked contractions of rat isolated uterine horn [41 ]. However, these responses are not affected by H, -receptor antagonists and have been defined as histamine H2-receptor responses following the development of specific antagonists to these responses such as burimamide [41], cimetidine [42] and ranitidine [43]. The distribution and classification of histamine H,-and H2-receptors in various mammalian peripheral tissues have been reviewed elsewhere [44-46a]. 

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