RECEPTORS INVOLVED IN NERVE-MEDIATED VASOCONSTRICTION IN SMALL ARTERIES OF THE RAT HEPATIC MESENTERY

1 We have investigated the neurotransmitters and receptor subtypes inv olved in nerve-mediated vasoconstriction in small arteries of the rat hepatic mesentery. 2 A dense sympathetic innervation was demonstrated using catecholamine histochemistry and antibodies against the synaptic vesicle protein synaptophysin. 3 Reverse transcription-polymerase cha in reaction (RT-PCR) demonstrated very strong expression of the alpha( 1A)-adrenergic, neuropeptide Y (NPY) Y-1, P-2X1- and P-2x4-purinergic receptors, moderate expression of the alpha(2B)-adrenergic receptor an d the purinergic P-2X5- and P-2x7-receptors and weak expression of the alpha(1B)-, alpha(1D)-, alpha(2A)- and alpha(2C)-adrenergic receptors and the P-2X2- and P-2X3-purinergic receptors. NPY2 and P-2X6 recepto r 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 benextrami ne (10(-5) M) and alpha,beta-methylene ATP, (alpha,beta-mATP, 3 X 10(- 6) M) or PPADS (10(-5) M). Selective alpha(1)-adrenergic receptor anta gonists showed the potency order of prazosin>WB-4101 > 5-methyl-urapid il> BMY 7378. Yohimbine (10(-8) M, 10(-7) M), alpha,beta-mATP (3 X 10( -6) M) and PPADS (10(-5) M) each enhanced the response to nerve stimul ation. 5 Some experiments demonstrated a slow neurogenic contraction w hich was abolished by GE or the selective NPY1 receptor antagonist 122 9U91 (6 X 10(-7) hr). 6 We conclude that nerve-mediated vasoconstricti on results from the activation of postsynaptic alpha(1A)-adrenergic an d P-2X-purinergic receptors and under some conditions, NPY1 receptors. Neurotransmitter release is modulated by presynaptic alpha(2)-adrener gic receptors and possibly also P-2X-purinoceptors. The major postsyna ptic subtypes involved were well predicted by mRNA expression as measu red by RT-PCR, suggesting that this technique may be a useful adjunct to studies aimed at identifying functional receptor subtypes.