Characterization of the endokinins: human tachykinins with cardiovascular activity.
We report four human tachykinins, endokinins A, B, C, and D (EKA-D), encoded from a single tachykinin precursor 4 gene that generates four mRNAs (alpha, beta, gamma, and delta). Tachykinin 4 gene expression was detected primarily in adrenal gland and in the placenta, where, like neurokinin B, significant amounts of EKB-like immunoreactivity were detected. EKA/B 10-mers displayed equivalent affinity for the three tachykinin receptors as substance P (SP), whereas a 32-mer N-terminal extended form of EKB was significantly more potent than EKA/B or SP. EKC/D, which possess a previously uncharacterized tachykinin motif, FQGLL-NH(2), displayed low potency. EKA/B displayed identical hemodynamic effects to SP in rats, causing short-lived falls in mean arterial blood pressure associated with tachycardia, mesenteric vasoconstriction, and marked hindquarter vasodilatation. Thus, EKA/B could be the endocrineparacrine agonists at peripheral SP receptors and there may be as yet an unidentified receptor(s) for EKC/D.
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Nigel M
NM
School of Animal and Microbial Sciences, University of Reading, United Kingdom.
Bell
Nicola J
NJ
Gardiner
Sheila M
SM
Manyonda
Isaac T
IT
Brayley
Kerensa J
KJ
Strange
Philip G
PG
Lowry
Philip J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001254:Astrocytoma; D001483:Base Sequence; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D016384:Consensus Sequence; D017931:DNA Primers; D005091:Exons; D005909:Glioblastoma; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015320:Tachykinins / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D015320:Tachykinins