title: A pharmacological investigation of the venom extract of the Australian box jellyfish, Chironex fleckeri, in cardiac and vascular tissues.
abstract: The pharmacology of Australian box jellyfish, Chironex fleckeri, unpurified (crude) nematocyst venom extract (CVE) was investigated in rat isolated cardiac and vascular tissues and in anaesthetised rats. In small mesenteric arteries CVE (0.01-30 μg/ml) caused contractions (EC(50) 1.15±0.19 μg/ml) that were unaffected by prazosin (0.1 μM), bosentan (10 μM), CGRP(8-37) (1 μM) or tetrodotoxin (1 μM). Box jellyfish antivenom (5-92.6 units/ml) caused rightward shifts of the CVE concentration-response curve with no change in the maximum. In the presence of l-NAME (100 μM) the sensitivity and maximum response to CVE were increased, whilst MgSO(4) (6 mM) decreased both parameters. CVE (1-10 μg/ml) caused inhibition of the contractile response to electrical sympathetic nerve stimulation. Left atrial responses to CVE (0.001-30 μg/ml) were bi-phasic, composed of an initial positive inotropy followed by a marked negative inotropy and atrial standstill. CVE (0.3 μg/ml) elicited a marked decrease in right atrial rate followed by atrial standstill at 3 μg/ml. These responses were unaffected by 1 μM of propranolol, atropine or CGRP(8-37). Antivenom (54 and 73 units/ml) caused rightward shifts of the CVE concentration-response curve and prevented atrial standstill in left and right atria. The effects of CVE do not appear to involve autonomic nerves, post-synaptic α(1)- or β(1)-adrenoceptors, or muscarinic, endothelin or CGRP receptors, but may occur through direct effects on the cardiac and vascular muscle. Box jellyfish antivenom was effective in attenuating CVE-induced responses in isolated cardiac and vascular tissues.
authors.affiliation: Cardiovascular Therapeutics Unit, Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia. r.hughes8@pgrad.unimelb.edu.au
authors.forename: Richard J A
authors.initials: RJ
authors.lastname: Hughes
authors.forename: James A
authors.initials: JA
authors.lastname: Angus
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Winkel
authors.forename: Christine E
authors.initials: CE
authors.lastname: Wright
mesh_terms: D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002395:Catecholamines / Q000032:analysis; D003064:Cnidarian Venoms / Q000737:chemistry / Q000633:toxicity*; D037462:Cubozoa / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004574:Electromagnetic Fields; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014020:Tissue Extracts / Q000737:chemistry / Q000633:toxicity
chemical_list: D000997:Antivenins; D002395:Catecholamines; D003064:Cnidarian Venoms; D014020:Tissue Extracts; D015740:Calcitonin Gene-Related Peptide