Ascaris GABA receptors

All cell membranes contain transmembrane proteins that form ion channels. These ion channels are usually selectively permeable to particular ions. Some channels, such as GABA-gated ion channels, are permeable to Cl ions and are inhibitory in nature because they make the inside of the nerve or muscle cells more negative as the Cl ions enter. Some ion channels are permeable to the cations Na and K, and an example of this type is the nicotinic acetylcholine-gated channel. Nicotinic channels have an excitatory effect when they open because Na ions enter and K ions leave through these channels. The cell becomes more positive inside and depolarizes. If the cell is a muscle cell, calcium accumulates in the cytoplasm and it contracts. We have found that all over the surface of Ascaris muscle there are GABA receptors (Martin, 1980) as well as nicotinic acetylcholine channels (Martin, 1982 Robertson and Martin, 1993). 

We have shown that the anthelmintics pyrantel, morantel and levamisole, activate acetylcholine (Ach) receptors on the muscle cell membranes of Ascaris suum and also that the avermectin 22,23-dihydroavermectin Bla (DHAVM) blocks the function of muscle cell gamma-aminobutyric acid (GABA) receptors. In experiments using micro-iontophoresis, the cholinergic anthelmintics were found to act directly on the muscle bag membrane, evoking a depolarizing response. 

Holden-Dye, L., Krogsgaard-Larsen, P., Neilsen, L. and Walker, R. J. (1989) GABA receptors on the somatic muscle cells of the parasitic nematode, Ascaris suum stereoselectivity indicates similarity to a GABA -type agonist recognition site. Br. J. Pharmacol. 98 841-850. 

Duittoz, A. H. and Martin, R. J. (1991) Effects of the arylaminopyrazine-GABA derivatives SR95103 and SR95531 on the Ascaris muscle GABA receptor the relative potency of the antagonists in Ascaris is different to that at vertebrate GABA receptors. Comp. Biochem. Physiol. 98C 417-422. 

Piperazine is highly effective against A. lumbricoides and E. vermicularis. The predominant effect of piperazine on Ascaris is a temporary paralysis that results in expulsion of the worm by peristalsis. Piperazine acts as a GABA-receptor agonist. By increasing Cl conductance of the Ascaris muscle membrane, the drug produces hyperpolarization that leads to flaccid paralysis. 

Mechanism Piperazine paralyzes ascaris by acting as an agonist at GABA receptors. The paralyzed roundworms are expelled live by normal peristalsis. 

Anthelmintics Affecting GABA and Acetylcholine Receptors on Ascaris Muscle Bags... 

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