J M Bowen1, R J Cole, D Bedell, D Schabdach. 1. Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Abstract
OBJECTIVE: To define the nature and mechanisms of neuromuscular effects of toxic principles in bark of Southern Prickly Ash tree (Zanthoxylum clava-herculis) that might contribute to its clinical toxicity in cattle. ANIMALS: 31 rats, 1 dog, and 4 rabbits. PROCEDURES: Extracts were prepared from bark samples, using 2 extraction methods. Contractile responses, resting potentials, miniature end-plate potentials (MEPP), and end-plate potentials of rat phrenic nerve-hemidiaphragm preparations were recorded. Blood pressure and contractile responses of the cranial tibial muscle to nerve stimulation were recorded in an anesthetized dog. Topical anesthetic activity in rabbits was determined by evaluation of the corneal reflex. RESULTS: One extract usually stimulated muscle contractile response, whereas the other inhibited this response when evoked by nerve stimulation, but not when evoked by direct muscle stimulation. Inhibitory extract (XI) had a hypotensive effect, but lacked topical anesthetic activity and effect on resting potentials. This extract also reduced amplitude of MEPP and end-plate potentials, but did not affect their time course or the frequency of MEPP. Stimulatory extract was not active in presence of neuromuscular blocking agent tubocurarine. CONCLUSION: Active principles in Southern Prickly Ash extracts appear to exert their action on neuromuscular transmission probably through blockade of postjunctional, end-plate receptors (XI) or enhanced release of neurotransmitter (stimulatory extract). CLINICAL RELEVANCE: Signs of clinical toxicity in cattle were best correlated with effects of XI, which can be antagonized by Ca2+ and neostigmine.
OBJECTIVE: To define the nature and mechanisms of neuromuscular effects of toxic principles in bark of Southern Prickly Ash tree (Zanthoxylum clava-herculis) that might contribute to its clinical toxicity in cattle. ANIMALS: 31 rats, 1 dog, and 4 rabbits. PROCEDURES: Extracts were prepared from bark samples, using 2 extraction methods. Contractile responses, resting potentials, miniature end-plate potentials (MEPP), and end-plate potentials of rat phrenic nerve-hemidiaphragm preparations were recorded. Blood pressure and contractile responses of the cranial tibial muscle to nerve stimulation were recorded in an anesthetized dog. Topical anesthetic activity in rabbits was determined by evaluation of the corneal reflex. RESULTS: One extract usually stimulated muscle contractile response, whereas the other inhibited this response when evoked by nerve stimulation, but not when evoked by direct muscle stimulation. Inhibitory extract (XI) had a hypotensive effect, but lacked topical anesthetic activity and effect on resting potentials. This extract also reduced amplitude of MEPP and end-plate potentials, but did not affect their time course or the frequency of MEPP. Stimulatory extract was not active in presence of neuromuscular blocking agent tubocurarine. CONCLUSION: Active principles in Southern Prickly Ash extracts appear to exert their action on neuromuscular transmission probably through blockade of postjunctional, end-plate receptors (XI) or enhanced release of neurotransmitter (stimulatory extract). CLINICAL RELEVANCE: Signs of clinical toxicity in cattle were best correlated with effects of XI, which can be antagonized by Ca2+ and neostigmine.