Receptors involved in nerve-mediated vasoconstriction in small arteries of the rat hepatic mesentery.
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 using catecholamine histochemistry and antibodies against the synaptic vesicle protein synaptophysin. 3. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated very strong expression of the alpha1A-adrenergic, neuropeptide Y (NPY) Y1, P2X1- and P2X4-purinergic receptors, moderate expression of the alpha2B-adrenergic receptor and the purinergic P2X5- and P2X7-receptors and weak expression of the alpha1B-, alpha1D-, alpha2A- and alpha2C-adrenergic receptors and the P2X2- and P2X3-purinergic receptors. NPY2 and P2X6 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 alpha,beta-methylene ATP, (alpha,beta-mATP, 3 x 10(-6) M) or PPADS (10(-5) M). Selective alpah1-adrenergic receptor antagonists showed the potency order of prazosin > WB-4101 > 5-methyl-urapidil > 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 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 alpha,beta-adrenergic and P2X-purinergic receptors and under some conditions, NPY1 receptors. Neurotransmitter release is modulated by presynaptic alpha2-adrenergic receptors and possibly also P2X-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.
Phillips
J K
JK
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT.
McLean
A J
AJ
Hill
C E
CE
D000818:Animals; D001483:Base Sequence; D002395:Catecholamines / Q000378:metabolism; D017931:DNA Primers; D004558:Electric Stimulation; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply* / Q000294:innervation / Q000378:metabolism; D008638:Mesenteric Arteries / Q000294:innervation / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000145:classification / Q000235:genetics / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D011983:Receptors, Purinergic / Q000145:classification / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D002395:Catecholamines; D017931:DNA Primers; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D017476:Receptors, Neuropeptide Y; D011983:Receptors, Purinergic