PURINERGIC and ADRENERGIC COTRANSMISSION IN CANINE ISOLATED and PERFUSED GASTROEPIPLOIC ARTERIES

Authors: Tanaka K.1; Yang X-P.1; Chiba S.1

Source: Clinical and Experimental Pharmacology and Physiology, Volume 30, Number 9, September 2003 , pp. 678-683(6)

Publisher: Blackwell Publishing

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Abstract:

Summary

1. The vasoconstrictor responses of canine gastroepiploic artery to periarterial electrical nerve stimulation (PNS; 30 s trains of pulses at a frequency of 2, 4 or 8 Hz) were observed in a frequency dependent manner. The PNS-induced vasoconstrictions were abolished by tetrodotoxin (1 µmol/L) and mostly depressed but not completely by guanethidine (10 µmol/L).

2. Vasoconstrictor responses to administered noradrenaline were antagonized significantly by prazosin (0.1 µmol/L), an agr1-adrenoceptor antagonist, but were not significantly affected by suramin (100 µmol/L), a P2 purinoceptor antagonist, or agr,bgr-methylene ATP (1 µmol/L), a P2X receptor desensitizing agent. Exogenous ATP-induced responses were clearly depressed by suramin or agr,bgr-methylene ATP, but were not significantly affected by prazosin.

3. The vasoconstrictor responses to PNS at a low frequency (2 and 4 Hz) of stimulation were markedly inhibited by suramin (100 µmol/L) and by agr,bgr-methylene ATP (1 µmol/L). The remaining responses after suramin or agr,bgr-methylene ATP were abolished by subsequent application of prazosin (0.1 µmol/L). At a high frequency (8 Hz) of stimulation, the vascular response was not significantly inhibited by suramin or agr,bgr-methylene ATP, but it was abolished by prazosin.

4. Injection of xylazine (0.3–30 nmol/L), an agr2-adrenoceptor agonist, did not induce any clear vasoconstriction. The exposure of tissues to rauwolscine (0.1–0.3 µmol/L), an agr2-adrenoceptor antagonist, dose-dependently increased PNS-induced vasoconstrictions at all frequencies tested.

5. The present results indicate that ATP acts as a cotransmitter with noradrenaline and is responsible for post-junctional vasoconstrictor responses at low frequencies of sitmulation, whereas the effect of noradrenaline is dominant at high-frequency stimulation in canine gastroepiploic artery. Prejunctional agr2-adrenoceptor autoinhibition may modulate the release of either noradrenaline or ATP from sympathetic nerve terminals.

Keywords: agr1-adrenoceptor; canine gastroepiploic artery; neurotransmission; P2X receptor; sympathetic nerve stimulation

Document Type: Research article

DOI: 10.1046/j.1440-1681.2003.03897.x

Affiliations: 1: Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan

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