Receptors involved in nerve-mediated vasoconstriction in small arteries of the rat hepatic mesentery

Jacqueline K. Phillips*, Allan J. McLean, Caryl E. Hill

*Corresponding author for this work

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

1. We have investigated the neurotransmitters and receptor subtypes involved in nerve-mediated vasoconstriction in small arteries of the rat hepatic mesentery. 2. A dense sympathetic innervation was demonstrated antibodies against the synaptic vesicle protein synaptophysin. 3. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated very strong expression of the α(1A)-adrenergic, neuropeptide Y (NPY) Y1, P(2X1)- and P(2X4)-purinergic receptors, moderate expression of the α(2B)-adrenergic receptor and the purinergic P(2X5)- and P(2X7)-receptors and weak expression of the α(1B)-, α(1D)-, α(2A)- and α(2C)-adrenergic receptors and the P(2X2)- and P(2X3)-purinergic receptors. NPY2 and P(2X6) receptor expression was absent. 4. Electrical field stimulation (10 Hz, 10 s) produced contractions which were abolished by tetrodotoxin (10-6 M) and/or guanethidine (GE, 5 x 10-6 M) and a combination of benextramine (10-5 M) and α,β-methylene ATP, (α,β-mATP, 3 x 10-6 M) or PPADS (10-5 M). Selective α1-adrenergic receptor antagonists showed the potency order of prazosin > WB-4101 > 5-methyl-urapidil > BMY 7378. Yohimbine (10-8 M, 10-7 M), α,β-mATP (3 x 10-6 M) and PPADS (10-5 M) each enhanced the response to nerve stimulation. 5. Some experiments demonstrated a slow neurogenic contraction which was abolished by GE or the selective NPY1 receptor antagonist 1229U91 (6 x 10-7 M). 6. We conclude that nerve-mediated vasoconstriction results from the activation of postsynaptic α(1A)-adrenergic and P(2X)-purinergic receptors and under some conditions, NPY1 receptors. Neurotransmitter release is modulated by presynaptic α2-adrenergic receptors and possibly also P(2X)-purinoceptors. The major postsynaptic subtypes involved were well predicted by mRNA expression as measured by RT-PCR, suggesting that this technique may be a useful adjunct to studies aimed at identifying functional receptor subtypes.

Original languageEnglish
Pages (from-to)1403-1412
Number of pages10
JournalBritish Journal of Pharmacology
Volume124
Issue number7
DOIs
Publication statusPublished - 1998
Externally publishedYes

Keywords

  • α(1A)-adrenoceptors
  • Neuropeptide Y receptors
  • P(2X)-purinoceptor
  • Presynaptic receptors
  • Receptor mRNA expression

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