Evidence that herbicides relaxing smooth and oblique-striated muscles affect the muscle cell membrane

1. From the example of two herbicides [chlorpropham (CIPC) and terbutryn], it has been shown that such compounds inhibit spontaneously occurring, as well as pharmacologically (ACh, KCl, caffeine) or electrically (negative DC) evoked tonic and phasic activities in different smooth and oblique-striated muscles of snails [penis retractor muscle (PRM) of Helix], worms (torsos and muscle segments of Lumbricus and Eisenia) and mice (small intestine of Mus). In PRM preparations, experiments with the denervating drugs 6-OHDA, -5,6-DHT, and reserpine, or with the serotonergic receptor blocker methysergide, produced evidence that the herbicidal side-effect was not caused by action on the nervous system. 3. A relaxant effect on ACh-evoked contractions in the PRM was induced by drugs altering the Ca2+ equilibrium, for example, theophylline, papaverine, chlorpromazine, or trifluoperazine. 4. In addition, an extracellular Ca2+ deficiency or the presence of papaverine led to an enhancement of a CIPC-caused inhibition of ACh- or KCl-induced contractions. 5. The amplitudes of chemically evoked contractions in "skinned muscle cells" of Helix PRM or Lumbricus segments were influenced neither by CIPC nor by terbutryn. 6. CIPC was concentrated by the intact PRM and by a membrane containing PRM fraction, as well as by the worms' circular muscle system. 7. A fluorescent CIPC analogue, dansyl-3-chloroaniline, characterized by a similar inhibiting property on the induced contractions was detected at the border of PRM cells. 8. It is concluded that in the different muscle systems the side-effect of the herbicidal compounds is located in the outer muscle cell membrane where a Ca2+-dependent mechanism may be concerned.