Motility inhibitory activity

Compounds 19 and 20 along with some acylated phosphatidic derivatives in addition to 1,2-dioleoylphosphatidic acid, were tested using the particle bioassay [83]. Commercially available l-oleoyl-2-lysophosphatidic acid (21) possessed repellent activity which was enhanced by monomethylation. When A. cochlioides zoospores were pre-treated with an excess of the natural stimulant N-frans-feruloyltyramine (19), and then exposed to Chromosorb W AW particles coated with various test compounds, it was found that 1 -oleoyl-2-lysophosphatidic (21, 100 ppm) and its monomethyl ester (22) (10 ppm), as well as the natural repellent 1-linoleoyl-2-lysophosphatidic acid monomethyl ester (20, 30 ppm), effectively inhibited zoospore motility [83], However, l-oleoyl-2-lysophosphatidic acid dimethyl ester (23) and 1,2-dioleoylphosphatidic acid tested with and without the stimulant (19) showed neither repellent nor motility inhibitory activity. The bioassay revealed that compounds possessing repellent activity are monoacylated phosphatidic acid derivatives containing at least one hydroxy group on the phosphoryl unit [83]. 

Lannea coromandelica L. (Anacardiaceae) is a deciduous tree widely distributed in Bangladesh, India and some other tropical countries. Plants belonging to this genus are used in folk medicine for treatment of elephantiasis, impotence, ulcers, vaginal troubles, halitosis, heart disease, dysentery, gout and rheumatism [108]. Stem bark extracts of L. coromandelica exhibited potent zoospore motility inhibitory activity followed by characteristic lysis. Identification of active principles and their mode of action toward zoospores are briefly discussed here. 

Cannabimimetics reduce the intestinal motility by a CB1-mediated inhibitory activity on acetylcholine release from autonomic fibers. An endo-cannabinoid, 2-AG, was isolated from dog intestine however, its role there remains unknown (Mechoulam, 1995a). 

Taurine (2-aminoethanesulfonic acid 4.235) is an inhibitory neurochemical that probably acts primarily as a neuromodulator rather than a neurotransmitter. It is formed from cysteine, and its accumulation can be prevented by the cardiac glycoside ouabain. Although receptor sites and specific actions cannot be elucidated without an antagonist, taurine has been implicated in epilepsy and, potentially, in heart disease. There are a large number of physiological effects attributed to taurine, among them cardiovascular (antiarrythmic), central (anticonvulsant, excitability modulation), muscle (membrane stabilizer), and reproductive (sperm motility factor) activity. Analogs of taurine, phthalimino-taurinamide (4.236) and its iV-alkyl derivatives, are less polar than taurine and are potent anticonvulsant molecules. 

Calponin is another polypeptide monomer (M.W. 32,000) that can inhibit actin-activated myosin ATPase activity. In contrast to CaD, CaP exerts its effect in the absence of tropomyosin and completely inhibits motility in a 2/3 ratio with actin. CaP inhibits myosin binding to actin, but does so by reducing the affinity of actin for myosin rather than competing for the same site. CaP can be phosphorylated by PKC and CaMKII, both of which reverse CaP s inhibitory activity. As with caldesmon, many questions remain. The ratio of CaP to actin actually observed in smooth muscle is in the range 1 10 to 1 16, far from the 2/3 ratio found to produce near-complete inhibition of motility. Therefore, the importance of CaP and its regulation by phosphorylation is still debatable. 

The same effect was observed in motility assays, where restoration of movement of actin over myosin required high concentrations (10 xM) of CaM (Shirinsky et al., 1992). CP can also be phosphoiylated in vitro and this phosphorylation abolishes its inhibitory activity (Winder and Walsh, 1990c). CP phosphorylation is considered in more detail in Section VI. 

Twenty nine steroidal saponins have been evaluated for their inhibitory effects on human spermatozoa motility in vitro according to a modified Sander-Cramer method [233]. Spirostane-type saponins have stronger inhibitory activities than those of furostane-type. The carbonyl group at C-12 and the double bond A (5,6) of the aglycone were important for the activity. The monodesmosidic saponin, diuranthoside B from Diuranthera major appeared the most active (motility of 45% at 0.1 mg/ml), almost equivalent to the commonly used spermicidal agent N-9. These results indicated the possibility of discovering natural spermicidal agents from steroidal saponins. Further work on the cytotoxic activity of these compounds are underway. 

Table 4. Motility Inhibitory and Zoospore Lytic Activities Induced by Ancardic Acids, Related Compounds and a Synthetic Pesticide...

In spite of the well documented inhibitory effects mediated by H3 receptors in electrically-stimulated preparations of the guinea pig intestine, the activation of this receptor subtype does not influence the reflex-evoked peristaltic motility of the guinea pig ileum (Poli et al., 1997 Poli and Pozzoli 1997). Since this experimental model reproduces peristalsis in quasi-physiologic conditions (Holzer, 1989), H3 receptors apparently play a minor role when compared to that of the other prejunctional receptors, such as a2-adrenoceptors and adenosine Ai-receptors, in the control of the physiologic motility of the gut (Figure 8). 

If an organ is innervated by both the sympathetic and parasympathetic divisions, a physiologic antagonism typically exists between these divisions. That is, if both divisions innervate the tissue, one division usually increases function, whereas the other decreases activity. For instance, the sympathetics increase heart rate and stimulate cardiac output, whereas the parasympathetics cause bradycardia. However, it is incorrect to state that the sympathetics are always excitatory in nature and that the parasympathetics are always inhibitory. In tissues such as the gastrointestinal tract, the parasympathetics tend to increase intestinal motility and secretion, whereas the sympathetics slow down intestinal motility. The effect of each division on any tissue must be considered according to the particular organ or gland. 

Thus, the motility of helminths is controlled by their neuromuscular system. Accordingly, the tone and activity of the longitudinal muscle fibres are controlled by neurotransmitters. There are two types of neurotransmitters, namely acetylcholine which works as an excitatory transmitter, and 4 (or y)-aminobutyric acid (GABA) which acts as an inhibitory transmitter. 

The predominant action of cannabinoid receptor agonists on the GI tract is an inhibitory effect on gastrointestinal motility, reminiscent of the neuromodulatory response to presynaptic p-opioid receptor or 02 -adrenoceptor activation of cholinergic, postganglionic parasympathetic neurons. The mechanisms underlying this effect have been studied chiefly in the GI tract of small rodents, but also in man and the pig. Here we shall review the findings of studies carried out in vitro (Sect. 3.1, below) and in vivo (Sect. 3.2). 

The parasympathetic nerves enhance both tone and motility and relax sphincters, thereby favoring intestinal transit Muscarinic antagonists produce prolonged inhibitory effects on the motor activity of the GI tract relatively large doses are needed to produce such inhibition. The complex myenteric nervous system can regulate motility independently of parasympathetic control, however (sss Chapter 6). 

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