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The Journal of General Physiology logoLink to The Journal of General Physiology
. 1993 Feb 1;101(2):271–296. doi: 10.1085/jgp.101.2.271

Actions of cholinergic drugs in the nematode Ascaris suum. Complex pharmacology of muscle and motorneurons

PMCID: PMC2216759  PMID: 8455017

Abstract

The cholinergic agonists acetylcholine (ACh), nicotine, and pilocarpine produced depolarizations and contractions of muscle of the nematode Ascaris suum. Dose-dependent depolarization and contraction by ACh were suppressed by about two orders of magnitude by 100 microM d- tubocurarine (dTC), a nicotinic antagonist, but only about fivefold by 100 microM N-methyl-scopolamine (NMS), a muscarinic antagonist. NMS itself depolarized both normal and synaptically isolated muscle cells. The muscle depolarizing action of pilocarpine was not consistently antagonized by either NMS or dTC. ACh receptors were detected on motorneuron classes DE1, DE2, DI, and VI as ACh-induced reductions in input resistance. These input resistance changes were reversed by washing in drug-free saline or by application of dTC. NMS applied alone lowered input resistance in DE1, but not in DE2, DI, or VI motorneurons. In contrast to the effect of ACh, the action of NMS in DE1 was not reversed by dTC, suggesting that NMS-sensitive sites may not respond to ACh. Excitatory synaptic responses in muscle evoked by depolarizing current injections into DE1 and DE2 motorneurons were antagonized by dTC; however, NMS antagonized the synaptic output of only the DE1 and DE3 classes of motorneurons, an effect that was more likely to have been produced by motorneuron conduction failure than by pharmacological blockade of receptor. The concentration of NMS required to produce these changes in muscle polarization and contraction, ACh antagonism, input resistance reduction, and synaptic antagonism was 100 microM, or more than five orders of magnitude higher than the binding affinity for [3H]NMS in larval Ascaris homogenates and adult Caenorhabditis elegans (Segerberg, M. A. 1989. Ph.D. thesis. University of Wisconsin-Madison, Madison, WI). These results describe a nicotinic- like pharmacology, but muscle and motorneurons also have unusual responses to muscarinic agents.

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Selected References

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  1. Aceves J., Erlij D., Martínez-Marañn R. The mechanism of the paralysing action of tetramisole on Ascaris somatic muscle. Br J Pharmacol. 1970 May;38(3):602–607. doi: 10.1111/j.1476-5381.1970.tb10601.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams M. E., O'Shea M. Peptide cotransmitter at a neuromuscular junction. Science. 1983 Jul 15;221(4607):286–289. doi: 10.1126/science.6134339. [DOI] [PubMed] [Google Scholar]
  3. BALDWIN E., MOYLE V. A contribution to the physiology and pharmacology of Ascaris lumbricoides from the pig. Br J Pharmacol Chemother. 1949 Jun;4(2):145–152. doi: 10.1111/j.1476-5381.1949.tb00527.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beld A. J., Ariëns E. J. Stereospecific binding as a tool in attempts to localize and isolate muscarinic receptors. Part II. Binding of (plus)-benzetimide, (minus)-benzetimide and atropine to a fraction from bovine tracheal smooth muscle and to bovine caudate nucleus. Eur J Pharmacol. 1974 Feb;25(2):203–209. doi: 10.1016/0014-2999(74)90051-x. [DOI] [PubMed] [Google Scholar]
  5. Brading A. F., Caldwell P. C. The resting membrane potential of the somatic muscle cells of Ascaris lumbricoides. J Physiol. 1971 Sep;217(3):605–624. doi: 10.1113/jphysiol.1971.sp009588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colquhoun L., Holden-Dye L., Walker R. J. The pharmacology of cholinoceptors on the somatic muscle cells of the parasitic nematode Ascaris suum. J Exp Biol. 1991 Jul;158:509–530. doi: 10.1242/jeb.158.1.509. [DOI] [PubMed] [Google Scholar]
  7. Culotti J. G., Klein W. L. Occurrence of muscarinic acetylcholine receptors in wild type and cholinergic mutants of Caenorhabditis elegans. J Neurosci. 1983 Feb;3(2):359–368. doi: 10.1523/JNEUROSCI.03-02-00359.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davis R. E., Stretton A. O. Passive membrane properties of motorneurons and their role in long-distance signaling in the nematode Ascaris. J Neurosci. 1989 Feb;9(2):403–414. doi: 10.1523/JNEUROSCI.09-02-00403.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davis R. E., Stretton A. O. Signaling properties of Ascaris motorneurons: graded active responses, graded synaptic transmission, and tonic transmitter release. J Neurosci. 1989 Feb;9(2):415–425. doi: 10.1523/JNEUROSCI.09-02-00415.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fosbraey P., Johnson E. S. Release-modulating acetylcholine receptors in cholinergic neurones of the guinea-pig ileum. Br J Pharmacol. 1980 Feb;68(2):289–300. doi: 10.1111/j.1476-5381.1980.tb10418.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hedlund B., Arhem P., Lorentz M., Sydbom A. Non-muscarinic effects of scopolamine on N1E-115 neuroblastoma cells. Acta Physiol Scand. 1986 May;127(1):127–132. doi: 10.1111/j.1748-1716.1986.tb07884.x. [DOI] [PubMed] [Google Scholar]
  12. Johnson C. D., Russell R. L. Multiple molecular forms of acetylcholinesterase in the nematode Caenorhabditis elegans. J Neurochem. 1983 Jul;41(1):30–46. doi: 10.1111/j.1471-4159.1983.tb11811.x. [DOI] [PubMed] [Google Scholar]
  13. Johnson C. D., Stretton A. O. Localization of choline acetyltransferase within identified motoneurons of the nematode Ascaris. J Neurosci. 1985 Aug;5(8):1984–1992. doi: 10.1523/JNEUROSCI.05-08-01984.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kass I. S., Stretton A. O., Wang C. C. The effects of avermectin and drugs related to acetylcholine and 4-aminobutyric acid on neurotransmission in Ascaris suum. Mol Biochem Parasitol. 1984 Oct;13(2):213–225. doi: 10.1016/0166-6851(84)90114-2. [DOI] [PubMed] [Google Scholar]
  15. Martin R. J. Electrophysiological effects of piperazine and diethylcarbamazine on Ascaris suum somatic muscle. Br J Pharmacol. 1982 Oct;77(2):255–265. doi: 10.1111/j.1476-5381.1982.tb09294.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. NORTON S., DE BEER E. J. Investigations on the action of piperazine on Ascaris lumbricoides. Am J Trop Med Hyg. 1957 Sep;6(5):898–905. doi: 10.4269/ajtmh.1957.6.898. [DOI] [PubMed] [Google Scholar]
  17. Natoff I. L. The pharmacology of the cholinoceptor in muscle preparations of Ascaris lumbricoides var. suum. Br J Pharmacol. 1969 Sep;37(1):251–257. doi: 10.1111/j.1476-5381.1969.tb09542.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pennington A. J., Martin R. J. A patch-clamp study of acetylcholine-activated ion channels in Ascaris suum muscle. J Exp Biol. 1990 Nov;154:201–221. doi: 10.1242/jeb.154.1.201. [DOI] [PubMed] [Google Scholar]
  19. Rosenbluth J. Ultrastructure of somatic muscle cells in Ascaris lumbricoides. II. Intermuscular junctions, neuromuscular junctions, and glycogen stores. J Cell Biol. 1965 Aug;26(2):579–591. doi: 10.1083/jcb.26.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rozhkova E. K., Malyutina T. A., Shishov B. A. Pharmacological characteristics of cholinoreception in somatic muscles of the nematode, Ascaris suum. Gen Pharmacol. 1980;11(1):141–146. doi: 10.1016/0306-3623(80)90023-3. [DOI] [PubMed] [Google Scholar]
  21. Schwartz E. A. Depolarization without calcium can release gamma-aminobutyric acid from a retinal neuron. Science. 1987 Oct 16;238(4825):350–355. doi: 10.1126/science.2443977. [DOI] [PubMed] [Google Scholar]
  22. Stretton A. O., Fishpool R. M., Southgate E., Donmoyer J. E., Walrond J. P., Moses J. E., Kass I. S. Structure and physiological activity of the motoneurons of the nematode Ascaris. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3493–3497. doi: 10.1073/pnas.75.7.3493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Walrond J. P., Stretton A. O. Excitatory and inhibitory activity in the dorsal musculature of the nematode Ascaris evoked by single dorsal excitatory motonerons. J Neurosci. 1985 Jan;5(1):16–22. doi: 10.1523/JNEUROSCI.05-01-00016.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. del Castillo J., Morales T. The electrical and mechanical activity of the esophageal cell of Ascaris lumbricoides. J Gen Physiol. 1967 Jan;50(3):603–629. doi: 10.1085/jgp.50.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]

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