Role of endogenous endothelins in catecholamine secretion in the rat adrenal gland

Takahiro Nagayama, Fumiyo Kuwakubo, Takayuki Matsumoto, Yasuo Fukushima, Makoto Yoshida, Mizue Suzuki-Kusaba, Hiroaki Hisa, Yasuo Matsumura, Tomohiko Kimura, Susumu Satoh

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

We investigated the role of endogenous endothelins in catecholamine secretion in response to transmural electrical stimulation in the retrogradely perfused rat adrenal gland. (R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl]amino-4-methyl-pentanoyl]amino-3-[3-(1-methyl-1H-indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid (FR139317; 0.03-3 μM), an endothelin ET(A) receptor antagonist, inhibited the electrical stimulation-induced epinephrine and norepinephrine output. Neither N-cis-2,6-dimethylpiperidinocarbonyl-L-γ-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine (BQ-788; 0.03-3 μM), an endothelin ET(B) receptor antagonist, nor phosphoramidon (1-100 mM), an endothelin-converting enzyme inhibitor, affected the catecholamine output responses. However, the inhibition by FR139317 of the catecholamine output responses was abolished by pretreatment with phosphoramidon (100 mM) or BQ-788 (3 μM). These results indicate that activation of endothelin ET(B) receptors by endogenous endothelins inhibits the catecholamine output responses under the condition in which endothelin ET(A) receptors are blocked. Exogenous endothelin-1 (1-100 nM) did not affect the catecholamine output responses, but it inhibited the responses under treatment with phosphoramidon and FR139317. Activation of endothelin ET(A) receptors may interfere with the endothelin ET(B) receptor-mediated inhibitory action on the neuronally evoked secretion of adrenal catecholamines. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
JournalEuropean Journal of Pharmacology
Volume406
Issue number1
DOIs
Publication statusPublished - 2000 Oct 6

Keywords

  • BQ-788
  • Endothelin-1
  • FR139317
  • Phosphoramidon
  • Transmural electrical stimulation

ASJC Scopus subject areas

  • Pharmacology

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