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Comments on Avery L et al. (2000) West Coast Worm Meeting "A Muscarinic Contribution to the Regulation of Feeding" (0)
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Avery L, & Steger KA (2000). A Muscarinic Contribution to the Regulation of Feeding presented in West Coast Worm Meeting. Unpublished information; cite only with author permission.
Acetylcholine (Ach) is essential for worms' survival and can stimulate feeding through nicotinic receptors on the pharyngeal muscle. However, we suspect that Ach affects the pharynx through muscarinic receptors as well. Worms that lack Ach (e.g. cha-1 mutants) have a more severe feeding defect than worms that lack pharyngeal nicotinic transmission (eat-2; eat-18). Atropine, a muscarinic antagonist, causes worms to appear starved, although it increases their pumping rate. Three ORFs in the worm genome closely resemble vertebrate muscarinic receptors: C15B12.5 (acm-1), F47D12.2 (acm-2) and C53A5.12 (acm-3). We have examined the expression of these three genes: all three are expressed in pharyngeal tissue (muscle, neurons or both) and in the extra-pharyngeal nerve ring. We have obtained mutant alleles of two putative muscarinic receptors: acm-1, and acm-2 (a gift from Stefan Eimer and Rolf Baumeister). The two mutations have very different effects on worm physiology. acm-2 worms are hypersensitive to aldicarb (an inhibitor of cholinesterase) and to nicotine. They pump more rapidly than wild type worms in the absence of drug, and decrease their pumping rate in the presence of atropine. We suspect that acm-2 mutants are defective in down-regulating nicotinic transmission. We hypothesize that acm-2, which is expressed in neurons both inside and outside the pharynx, acts as a negative regulator at nicotinic synapses. acm-1 mutants, in contrast, are resistant to aldicarb, and are not hypersensitive to nicotine. In an unc-17 background of reduced cholinergic transmission, acm-1 worms are hypersensitive to atropine. We suspect that acm-1, probably in combination with acm-3, affects pumping efficiency or the adaptation of feeding behavior to particular circumstances. We are currently designing assays and appropriate genetic backgrounds to examine these possibilities