Nonadrenergic contractile response of guinea pig portal vein to electrical field stimulation mimics response to UTP but not to ATP

Michiyo Ishizaki, Yasutaka Iizuka, Mizue Suzuki-Kusaba, Tomohiko Kimura, Susumu Satoh

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Transmural electrical field stimulation (EFS, 4-32 Hz) produced a biphasic contractile response consisting of a rapid and transient contraction (first phase) followed by a slow contraction (second phase) in ring preparations of guinea pig portal veins. Both contractions were enhanced by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L- NAME, 30 μM). In the presence of L-NAME, tetrodotoxin (1 μM) and guanethidine (3 μM) inhibited both contractions and phentolamine (10 μM), and reserpine treatment abolished the first-phase contraction without affecting the second-phase contraction. These results suggest that the first- phase contraction is caused by norepinephrine released from the perivascular nerves. In the presence of phentolamine and L-NAME, the second-phase contraction was inhibited by the nonselective P2-purinoceptor antagonist suramin (30-300 μM) and the P(2Y)-purinoceptor antagonist reactive blue 2 (RB2; 10-100 μM). αβ-Methylene-adenosine triphosphate (α,β-mATP; 3-30 μM), which desensitizes P(2X)-purinoceptors, and the P(2X)-purinoceptor antagonist 4,4'-diisothiocyanatostilbene-2,2'-disulphonate (DIDS; 1-10 μM) had a little effect. Exogenous ATP (0.1-3 mM) and UTP (0.1-3 mM) in the presence of L-NAME produced contractions in a concentration-dependent manner. The ATP-induced contraction was enhanced by suramin, RB2, and DIDS but unaltered by α,β-mATp. The UTP-induced contraction was inhibited by suramin and RB2 but unaltered by α,β-mATP and DIDS. These results indicate that in the guinea pig portal vein, the classic P(2X)-purinoceptors do not contribute to the nonadrenergic component of sympathetic neurotransmission. Furthermore, the pharmacology of the nonadrenergic component of neurotransmission resembles that of vasoconstrictor responses to exogenous UTP rather than to ATP.

Original languageEnglish
Pages (from-to)360-366
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume29
Issue number3
DOIs
Publication statusPublished - 1997 Mar 1

Keywords

  • ATP
  • DIDS
  • Nonadrenergic contraction
  • Portal vein
  • Reactive blue 2
  • Suramin
  • Sympathetic nerve stimulation
  • UTP
  • α,β-methylene-ATP

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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