Toad

About: Toad is a research topic. Over the lifetime, 1624 publications have been published within this topic receiving 28732 citations.

Ouabain-like activity in toad skin and its implications for endogenous regulation of ion transport

Abstract: THE demonstration that opium alkaloids of the plant kingdom mediate their effects on animals through specific receptors1 led to the discovery that endogenous molecules with opiate activity exist widely in animals2, including man. These studies raised the possibility that other potent pharmacological agents derived from plant sources might have active analogues in higher species. Thus, cardiac glycosides are found widely in the plant kingdom3; structurally similar compounds in the animal kingdom are known to exist only in the poison glands of certain toads3. The dried skins of Bufonid toads have been used in Chinese folk medicine for the treatment of cardiac failure4. Further, these poorly characterised medicinal preparations (Ch'an Su) were shown in the 1920s to contain ouabain-like compounds (bufotoxins) by chemical analysis5. However, although bufotoxins were shown to be a major constituent of the poison glands of Bufo marinus3 the possibility that similar compounds might also serve a physiological role apart from that of a defensive toxin was apparently not considered. More recently, two major observations make the consideration of such a physiological role seem reasonable. First, amphibian skin, which is a major organ for regulation of sodium and water homeostasis in these species6, has been shown to be rich in (Na+ + K+)-ATPase, the molecular mediator of sodium transport across the skin8. In fact, with toad bladder, amphibian skin has been widely used as a model of transepithelial ion transport in higher animals. Second, the pharmacological receptor for cardiac glycosides is now believed to be the (Na+ + K+)-ATPase9,10, glycoside binding to this enzyme resulting in inhibition of both ATPase activity11,12 and associated ion transport13,14. This glycoside–enzyme interaction is considered to be the basis for the cardiac stimulating activity10 for which glycosides such as ouabain and digoxin are used in the therapy of cardiac disorders. We report here that extracts of the skin of three different species of toad each contain high concentrations of a substance with all the functional properties of cardiac glycosides. The widespread existence of ouabain-like activity in an organ rich in physiologically important (Na+ + K+)-ATPase suggests a possible role for these endogenous compounds in the regulation of transepithelial ion transport.

Effect of inorganic complex ions on transmission at a neuromuscular junction.

Abstract: SOME aspects of the chemical and biological activity of the inorganic complex ions have been previously reported by Beccari1 and by Dwyer and co-workers2–4. These workers have indicated that the complex cations show extremely high chemical stability, and most probably pass through the body unchanged. They also exhibit marked biological activity4, and when injected intraperitoneally into mice2 cause paralysis and death by respiratory failure suggestive of curariform activity. We have investigated their pharmacological mode of action on the rat diaphragm–phrenic nerve and toad (Bufo marinus) rectus abdominis muscle preparations. Investigations have also been carried out, in collaboration with Dr. Rosamond M. Eccles, of the Department of Physiology, Australian National University, using the toad sartorius nerve–muscle preparation and the isolated superior cervical ganglion of the rabbit.

A Sensitive Hydroosmotic Toad Bladder Assay : Affinity and intrinsic activity of neurohypophyseal peptides

Abstract: A sensitive and precise method for assaying the water permeability response evoked by neurohypophyseal hormones and their synthetic analogues on the isolated urinary bladder of the toad (Bufo marinus L.) is described. The method permits detection of 8-arginine-vasotocin at concentrations as low as 10-12M. This sensitivity, not achieved heretofore with this tissue, results largely from minimizing interference of inhibitory substances by means of an "in vitro circulation assembly." The precision of the method derives from a direct comparison between the cumulative dose-response curve of an agonist of unknown potency acting on one hemibladder and that of a reference compound acting on the contralateral hemibladder. Crystalline deamino-oxytocin is used as the reference standard in this assay. The intrinsic activity of 2-(O-methyltyrosine)-oxytocin, as defined by the maximal response, is 12% lower than that of deamino-oxytocin. All other hormonal peptides investigated have the same intrinsic activity as deamino-oxytocin, even 5-valine-oxytocin, in spite of its extremely low affinity. A comparison of the potencies of 8-arginine-vasotocin vs. 8-arginine-vasopressin, 8-ornithine-vasotocin vs. 8-ornithine-vasopressin, 8-alanine-oxytocin vs. 8-alanine-oxypressin, and deamino-8-alanine-oxytocin vs. deamino-8-alanine-oxypressin suggests that an isoleucine residue in position 3 imparts a higher specificity for binding of the hormonal peptide molecule to the bladder receptor than a phenylalanine residue in this locus.

Relevance of sodium transport pool measurements in toad bladder tissue for the elucidation of the mechanism whereby hormones stimulate active sodium transport

Abstract: The size of toad bladder sodium transport pool, defined as that amount of sodium of apical origin and recovered in tissue at equilibrium, was compared with sodium transport rate, derived from short-circuit current read immediately before tissue analysis. Provided certain precautions be taken, the relationship between both variables can be described by a curve starting at the intersect ofX (pool, in μEq) andY (transport, in μEq/hr) axes, with a tendency forX to increase faster thanY. Assuming sodium transport pool forms one compartment, its calculated half-life averages 2–3 min. sodium transport pool measurements are thought to shed light on mechanism of sodium transport by toad bladder because pool size was large with respect to transport rate when tissue was exposed to several inhibitors of sodium transport. Conversely, upon stimulation of activity of (substrate — depleted) preparations by glucose, a relative reduction of pool size was observed. Aldosterone, vasopressin (and adenosine 3′,5′-phosphate) increased sodium pool size and transport rate, proportionately; insulin stimulated sodium transport more than it increased pool size. Thus, insulin presumably exerts its effect at the sodium “pump” while such a site of action need not be postulated for aldosterone and vasopressin: these 2 hormones would instead induce, permeability changes faciliting sodium movement at the apical border of toad bladder epithelial cells.