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Interactions between neuropeptide Y and the adenylate cyclase pathway in rat mesenteric small arteries: role of membrane potential
Author(s) -
Prieto Dolores,
Buus Carsten,
Mulvany Michael J.,
Nilsson Holger
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.281bk.x
Subject(s) - hyperpolarization (physics) , forskolin , charybdotoxin , medicine , endocrinology , chemistry , glibenclamide , isoprenaline , membrane potential , mesenteric arteries , apamin , depolarization , acetylcholine , potassium channel , biology , artery , biochemistry , stimulation , organic chemistry , nuclear magnetic resonance spectroscopy , diabetes mellitus
1 Simultaneous measurements of membrane potential and tension were performed to investigate the intracellular mechanisms of neuropeptide Y (NPY) in rat mesenteric small arteries. 2 NPY (0.1 μ M )depolarized arterial smooth muscle cells from −55 to −47 mV and increased wall tension by 0.22N m −1 , representing 11% of the contraction elicited by a high potassium solution. Isoprenaline (1 μ M ) and acetylcholine (1 μ M ) evoked hyper polarizations of 11 and 17 mV, resupectively. NPY inhibited the isoprenaline ‐induced effects on membrane potential without affecting those of acetylcholine. 3 Forskolin evoked sustained concentration‐dependent hyper polarizations of small mesenteric arteries. NPY (0.1 m M ) inhibited the resuponses to 1 μ M forskolin, but did not alter the stable hyperpolarization elicited by the supecific activator of protein kinase A (PKA) S P ‐5,6‐DCl‐cBIMPS (0.1 mm). Forskolin increased the cyclic AMP (cAMP) content of the arteries 21‐fold, and NPY inhibited the forskolin‐evoked increase in cAMP levels by 91 %. 4 The hyperpolarization produced by 1 μ M forskolin was not affected by either charybdotoxin (0.1 μ M ) or 4‐aminopyridine (0.5mM), but glibenclamide (5 μ M ) inhibited the hyperpolarization by 70%. Glibenclamide also inhibited the hyperpolarization evoked by S P ‐:5,6‐DCl‐cBIMPSuby59%. 5 Neither depolarization nor contraction caused by NPY were significantly affected by either glibenclamide (5 μ M ) or nifedipine (1 μ M ), but they were reduced by gadolinium (10 μ M ). However, the blocking effect of NPY on forskolin‐elicited hyperpolarization was not affected by gadolinium. 6 Charybdotoxin (O.1 μ M ) and 4‐aminopyridine (0.5 m M ) strongly enhanced the depolarization and contraction caused by NPY (O.1μ M ), and nifedipine (1 μ M ) prevented the enhanced resuponses to NPY in the presence of charybdotoxin. 7 These findings suggest that NPY acts through at least two different intracellular mechanisms in mesenteric small arteries: a depolarization of arterial smooth muscle which is probably due to activation of non‐selective cation channels, and a marked inhibition of adenylate cyclase activity, which in turn inhibits the hyperpolarization produced by cAMP accumulation in these arteries.