title: Cloning and characterisation of natriuretic peptides from the venom glands of Australian elapids.
abstract: The venom from Australian elapid snakes contains a complex mixture of polypeptide toxins that adversely affect multiple homeostatic systems within their prey in a highly specific and targeted manner. Included in these toxin families are the recently described venom natriuretic peptides, which display similar structure and vasoactive functions to mammalian natriuretic peptides. This paper describes the identification and detailed comparative analysis of the cDNA transcripts coding for the mature natriuretic peptide from a total of nine Australian elapid snake species. Multiple isoforms were identified in a number of species and represent the first description of a natriuretic peptide from the venom gland for most of these snakes. Two distinct natriuretic peptide isoforms were selected from the common brown snake (Pseudonaja textilis), PtNP-a, and the mulga (Pseudechis australis), PaNP-c, for recombinant protein expression and functional analysis. Only one of these peptides, PtNP-a, displayed cGMP stimulation indicative of normal natriuretic peptide activity. Interestingly, both recombinant peptides demonstrated a dose-dependent inhibition of angiotensin converting enzyme (ACE) activity, which is predictive of the vasoactive effects of the toxin. The natriuretic peptides, however, did not possess any coagulopathic activity, nor did they inhibit or potentiate thrombin, adenosine diphosphate or arachidonic acid induced platelet aggregation. The data presented in this study represent a significant resource for understanding the role of various natriuretic peptides isoforms during the envenomation process by Australian elapid snakes.
authors.affiliation: The Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Liam
authors.initials: L
authors.lastname: St Pierre
authors.forename: Simone
authors.initials: S
authors.lastname: Flight
authors.forename: Paul P
authors.initials: PP
authors.lastname: Masci
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Hanchard
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lewis
authors.forename: Paul F
authors.initials: PF
authors.lastname: Alewood
authors.forename: John
authors.initials: J
authors.lastname: de Jersey
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
mesh_terms: D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D006152:Cyclic GMP / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D017815:Elapidae / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D018076:DNA, Complementary; D004546:Elapid Venoms; D045265:Natriuretic Peptides; D011994:Recombinant Proteins; D007703:Peptidyl-Dipeptidase A; D006152:Cyclic GMP