Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-6-2
pubmed:abstractText
Endothelins (ETs) and sarafotoxins (SRTXs) are active isopeptides that have very similar structures and functions. All isoforms interact with two specific G-protein-coupled receptors, ET(A) and ET(B). To characterize functional vascular ET receptors in the poisonous snake, Bothrops jararaca, cumulative concentration-response curves to ETs and SRTXs were performed in isolated aortic rings, in the absence and presence of selective ET receptor antagonists. Vascular expression of ET receptor messenger RNA (mRNA) was evaluated by reverse transcriptase (RT) polymerase chain reaction (PCR) analysis, and a fragment of the ET(A) receptor was cloned and sequenced. In vivo, ET-1 induced a dose-dependent biphasic response on anesthetized B. jararaca snakes. In vitro, ET-1, SRTX-b, ET-3, SRTX-c, and IRL-1620 induced concentration-dependent vasoconstriction, with a potency order suggesting the presence of typical ET(A) receptors. BQ-123, a selective ET(A) antagonist, inhibited contractions induced by ET-1 and SRTX-b with expected negative log of the dissociation constant, K(B), (pK(B)) values for mixed ET(A)/ET(B) receptor populations. The nonselective ET(A)/ET(B) receptors antagonist, PD-142893, produced similar inhibition. The ET(B) antagonist, IRL-1038, potentiated contractile responses to SRTX-c. ET-1 and SRTX-c responses were also potentiated when aortic rings were pretreated with N(omega)-nitro-L-arginine methyl ester (L-NAME) plus indomethacin. Processing of the B. jararaca aortic first-strand complementary DNA, by RT-PCR with primers designed from the Gallus gallus ET(A) receptor sequence, enabled isolation, purification, cloning, and sequencing of a single band. The partial sequence of the B. jararaca ET(A) receptor showed a very high sequence similarity with ET(A) receptor sequences from chicken, rat, human, and Xenopus. In conclusion, vascular responses to SRTXs/ETs in the B. jararaca aorta are mediated predominantly, but not exclusively, by typical ET(A) receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1535-3702
pubmed:author
pubmed:issnType
Print
pubmed:volume
231
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
729-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16740989-Amino Acid Sequence, pubmed-meshheading:16740989-Animals, pubmed-meshheading:16740989-Aorta, Thoracic, pubmed-meshheading:16740989-Base Sequence, pubmed-meshheading:16740989-Blood Pressure, pubmed-meshheading:16740989-Bothrops, pubmed-meshheading:16740989-Conserved Sequence, pubmed-meshheading:16740989-Crotalid Venoms, pubmed-meshheading:16740989-DNA, Complementary, pubmed-meshheading:16740989-Dose-Response Relationship, Drug, pubmed-meshheading:16740989-Female, pubmed-meshheading:16740989-Infusions, Intravenous, pubmed-meshheading:16740989-Male, pubmed-meshheading:16740989-Molecular Sequence Data, pubmed-meshheading:16740989-Muscle, Smooth, Vascular, pubmed-meshheading:16740989-Muscle Contraction, pubmed-meshheading:16740989-Perfusion, pubmed-meshheading:16740989-RNA, Messenger, pubmed-meshheading:16740989-Receptor, Endothelin A, pubmed-meshheading:16740989-Sequence Homology, Amino Acid, pubmed-meshheading:16740989-Sequence Homology, Nucleic Acid, pubmed-meshheading:16740989-Vasoconstriction, pubmed-meshheading:16740989-Vasoconstrictor Agents
pubmed:year
2006
pubmed:articleTitle
Pharmacologic and molecular characterization of the vascular ETA receptor in the venomous snake Bothrops jararaca.
pubmed:affiliation
Laboratory of Pharmacology, Butantan Institute, Av. Vital 1500, 05503-900 Sao Paulo, Brazil. rosabbor-gheresi@butantan.gov.br
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't