mise à jour du
22 mars 2009
Pharmacol Biochem Behav
Xenopus Skin Mucus Induces Oral Dyskinesias
That Promote Escape From Snakes
George T Barthalmus, William J Zielinski
Department of Zoology, North Carolina State University, Raleigh


African clawed frogs fed to American water snakes induced yawning and gaping which slowed ingestion and facilitated the frogs' escape without inducing flavor aversion. The peptide and/or indolealkylamine contents of the frog's poison glands caused the effect because frogs with purged glands did not induce these behaviors and rarely escaped. Poison gland mucus, applied orally, elicited similar oral movements. The frog's clear lubricating mucus was inactive. As several compounds in the poison glands have known neuroleptic properties, the oral behaviors may be induced by neural mechanisms reported to govern neuroleptic-induced orofacial dyskinesia in schizophrenics.
The skin secretions of many amphibians contain peptides that are identical to, or close analogues of, peptides found in the vertebrate brain and gut. Despite studies on peptides that form this "brain-gut-skin triangle", little is known of their role within amphibian skin. As poison glands of the African clawed frog (Xenopus !aevis) contain only peptides and indolealkylamines, we explored the potential antipredatory role of these compounds by feeding Xenopus to American northern water snakes (Nerodia sipedon). Here we report that such feedings cause dyskinetic yawning and gaping movements in the snake that frequently permitted a frog's escape. The dyskinesia is predictable given the known actions of each skin compound and their coincidence with neural mechanisms believed to underly drug- and peptide- induced oral dyskinesias in mammals including man.
Only toxic mucus consistently induced yawning and gaping. Fixed yawns and gapes (lasting >4.0 sec) were common in toxic mucus trials. Snakes yawned and gaped usually after having climbed the tank walls. Some fixed yawns and gapes occurred under water suggesting that yawning and gaping need not be associated with breathing. We conclude that toxic mucus induced involuntary yawning and gaping and permitted frogs to escape because few oral behaviors appeared in snakes given other mucus treatments.
Xenopus skin mucus contains the indolealkylamines, serotonin (5-HT) and bufotenidine (BF), and the following peptides: cholecystokinin octapeptide (CCK-8); caerulein (CRL), a close structural and functional analogue of CCK-8; r thyrotropin-releasing hormone (TRH); and xenopsin (XN), an analogue of neurotensin. Curiously, the action of each compound is compatible with hypotheses governing the tardive dyskinesias (TD) seen in schizophrenics treated chronically with dopaminergic blockers (the neuroleptics).
TD is an extrapyramidal dysfunction in which involuntary yawning, chewing and tongue movements occur. However, as dopamine inhibits release of tuberoinfundibular peptide hormones, the neuroleptics also elevate plasma levels of prolactin and oxytocin, alphamelanocyte stimulating hormone and adrenocorticotropin, which have all induced yawning in lab animals. As CCK-8 and CRL and 5-HT have neuroleptic properties, and XN may possess the neuroleptic properties of neurotensin, we suspect that these Xenopus skin compounds mimic neuroleptics and create a neurochemistry for oral dyskinesia in snakes that promotes the escape of frogs.
Further, 5-HT and bufotenidine and TRH elevate serum prolactin levels and oxytocin, the most potent known inducer of yawning, is dramatically elevated in plasma of rats administered CCK.
Our observation that oral dyskinesias occur within 30 seconds of oral contact with mucus suggests that toxins are absorbed orally and/or react with oral receptors. The snake's vomeronasal organ (VNO), a contact receptor that mediates detection of prey and the rate of tongue flicking, is probably not the chief target for skin toxins because two snakes given VNO nerve transections (but unconfirmed histologically) exhibited all presurgical dyskinesias.
This new behavioral model of orofacial dyskinesia appears biomedically promising given that the known compounds in Xenopus skin occur naturally in the mammalian brain or occur as close analogues of neurochemicals. Whether skin agents act in combinations or alone is the focus of our future studies. We are now assessing the behavioral responses of Lycodonomorphus rufulus, a natural snake predator of Xenopus in South Africa (J. Visser, personal communication). Typically, sympatric predator and prey species coevolve adaptations to each other's defenses. Thus, if African water snakes prove unresponsive to Xenopus' skin mucus, and if this defense is neurologic, such as an unusual profile of neurotransmitters typically affected by neuroleptics, rapid advances in drug development can be made by comparing the brain chemistry of Nerodia with that of Lycoodonomorphus.
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