Expression and function of neuronal nicotinic ACh receptors in rat microvascular endothelial cells

Moccia, Francesco; Frost, Christine; Berra‐Romani, Roberto; Tanzi, Franco; Adams, David J.

doi:10.1152/ajpheart.00620.2003

Cited by 55 publications

(47 citation statements)

References 28 publications

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“…7) Amounts of the a5 and a7 transcripts in BBMEC may not reach the detectable level in the present condition. On the other hand, slightly different expression patterns have been reported in rat coronary microvascular endothelial cells (a2, a3, a4, a5, a7, b2 and b4 subunits) 22) and in human aortic endothelial cells (a3, a5, a7, b2 and b4 subunits). 5,6) In contrast to the cerebral endothelial cells, these peripheral endothelial cells seem to express the b4-containing nicotinic receptor which is less sensitive to desensitization than the b2-containing and the a7-containing nicotinic receptors.…”

Section: Discussionmentioning

confidence: 88%

Nicotinic Enhancement of Proliferation in Bovine and Porcine Cerebral Microvascular Endothelial Cells

Tsuneki

Ito

Sekizaki

et al. 2004

Biological & Pharmaceutical Bulletin

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Neuronal nicotinic acetylcholine receptors are widely distributed in the brain. 1) They are pentameric ligand-gated ion channels made up of a combination of twelve different subunits (a2-a10, b2-b4).2,3) The nicotinic receptors are involved in cognitive processes such as learning and memory in the cerebral cortex and hippocampus. 4) Recently, the neuronal nicotinic receptors have been found in many non-neuronal cells, including peripheral and cerebral vascular endothelial cells. [5][6][7] It has been shown that nicotine stimulates DNA synthesis, proliferation and tube formation through activation of nicotinic receptors in bovine pulmonary artery endothelial cells, human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells. [8][9][10] These observations indicate that nicotinic receptors in the peripheral endothelial cells can contribute to angiogenesis in which new blood vessels are formed from pre-existing vasculatures. It is well known that the endothelial cells display remarkable heterogeneity in different organs.11,12) Therefore, an important and incompletely solved question is whether nicotinic receptors play a role in the cerebral angiogenesis, as well as the promotion of angiogenic processes in the peripheral vascular endothelial cells.The cerebral angiogenesis occurs in hypoxic and/or ischemic conditions, particularly in infarctions and infectious processes, to ameliorate the already disturbed brain conditions, whereas the angiogenesis exacerbates malignant glioma via increase in blood supply.13) Because the endothelial cell proliferation is a crucial step of angiogenesis, we investigated whether nicotinic stimulation promotes the proliferation of bovine and porcine cerebral microvascular endothelial cells. MATERIALS AND METHODS MaterialsAll drugs used were purchased from Sigma (St. Louis, MO, U.S.A.), unless indicated. Hexamethonium was purchased from Wako Pure Chemicals (Osaka, Japan). A rabbit anti-p44/p42 mitogen-activated protein (MAP) kinase antibody and a rabbit anti-phospho-p44/p42 MAP kinase antibody were purchased from Cell Signaling Technology (Beverly, MA, U.S.A.).Isolation of Brain Microvessels We adopted the previously described procedures 14) for isolation of bovine brain microvessel endothelial cells (BBMEC) and porcine brain microvessel endothelial cells (PBMEC). In brief, cerebrocortical regions were isolated from bovine and porcine brains, and gray matter was collected and homogenized in Dulbecco's modified Eagle medium (DMEM) containing 10% fetal bovine serum (FBS). Microvessel fragments were trapped on 150-mM nylon meshes, and were digested in collagenase type III (Gibco BRL, Life Technologies, Rockville, MD, U.S.A.), trypsin (Worthington Biochemical, Lakewood, NJ, U.S.A.) and DNase I (Worthington Biochemical) in 10% FBS-containing DMEM for 1 h at 37°C. After removal of debris using 200-mm nylon mesh, the brain microvessel fractions were resuspended in FBS with 10% dimethyl sulfoxide, and stored in liquid nitrogen until use.Culture of Endothelial Cells ...

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Section: Discussionmentioning

confidence: 88%

Nicotinic Enhancement of Proliferation in Bovine and Porcine Cerebral Microvascular Endothelial Cells

Tsuneki

Ito

Sekizaki

et al. 2004

Biological & Pharmaceutical Bulletin

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“…The presence of ␣ and ␤ subunits not previously reported to be expressed in adrenal medullary tissue could reflect a unique fetal pattern of expression. As a word of caution in interpreting these findings, the presence of vascular components such as endothelial cells, vascular smooth muscle, and cortex in the tissue preparation could contribute to the detection of these subunits (30). The decreased expression of nicotinic receptor subunits in the LTH fetal adrenal implicates a decreased capacity to respond to cholinergic stimuli as a potential mechanism leading to the decreased expression of all three enzymes mediating catecholamine synthesis.…”

Section: Discussionmentioning

confidence: 99%

Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus

Ducsay¹,

Hyatt²,

Młynarczyk³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Ducsay CA, Hyatt K, Mlynarczyk M, Root BK, Kaushal KM, Myers DA. Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus. Am J Physiol Regul Integr Comp Physiol 293: R1997-R2005, 2007. First published August 15, 2007; doi:10.1152/ajpregu.00313.2007.-We previously communicated that long-term hypoxia (LTH) resulted in a selective reduction in plasma epinephrine following acute stress in fetal sheep. The present study tested the hypothesis that LTH selectively reduces adrenomedullary expression of phenylethanolamine-N-methyltransferase (PNMT), the rate-limiting enzyme for epinephrine synthesis. We also examined the effect of LTH on adrenomedullary nicotinic, muscarinic, and glucocorticoid receptor (GR) expression. Ewes were maintained at high altitude (3,820 m) from 30 to 138 days gestation (dGA); adrenomedullary tissue was collected from LTH and age-matched, normoxic control fetuses at 139 -141 dGA. Contrary to our hypothesis, in addition to PNMT, adrenomedullary expression (mRNA, protein) of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) were reduced in the LTH fetus. Immunocytochemistry indicated that TH and DBH expression was lower throughout the medulla, while PNMT appeared to reflect a reduction in PNMT-expressing cells. Nicotinic receptor alpha 1, 2, 3, 5, 6, 7, beta 1, 2, and 4 subunits were expressed in the medulla of LTH and control fetuses. Messenger RNA for alpha 1 and 7 and beta 1 and 2 subunits was lower in LTH fetuses. Muscarinic receptors M1, M2, and M3 as well as the GR were also expressed, and no differences were noted between groups. In summary, LTH in fetal sheep has a profound effect on expression of key enzymes mediating adrenomedullary catecholamine synthesis. Further, LTH impacts nicotinic receptor subunit expression potentially altering cholinergic neurotransmission within the medulla. These findings have important implications regarding fetal cardiovascular and metabolic responses to stress in the LTH fetus. adrenal; ovine; catecholamine BY LATE GESTATION IN THE DEVELOPING ovine fetus, stress activates the sympathetic nervous system, eliciting the release of both norepinephrine and epinephrine. These catecholamines play an essential role in regulating fetal cardiovascular and metabolic responses to a wide variety of stresses and are fundamental in the adaptation of the neonate to the extrauterine environment postbirth (12,35,36). As observed in the adult, the adrenal medulla is the major source of both basal and stress-induced epinephrine in the circulation and contributes significantly to plasma norepinephrine concentrations in the late-gestation ovine fetus (12,25,34,35). There is evidence that both structural and functional innervation of the adrenal medulla occurs during the final third of gestation as the fetus prepares for birth with synapses between splanchnic cholinergic nerve terminals and adrenal chromaffin cells developing between 100 and 130 days of gestation (dGA; term is ϳ148 dGA) in fetal sheep ...

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“…Intracellular mechanisms that are activated by nicotine in endothelial cells have been demonstrated by Di Luozzo et al 109 and include MAPKs p38 and p44/p42. The receptors present on rat endothelial cells, as revealed 110 by RT-PCR include nAChRs a 2, a 3, a 4, a 5, a 7, b 2, and b 4 but not b 3. Saeed et al 111 have demonstrated that nicotine inhibits the expression of endothelial adhesion molecules, suggesting that the effect of nicotine on these cells is anti-infl ammatory.…”

Section: Endotheliummentioning

confidence: 97%

Neuronal nicotinic acetylcholine receptor expression and function on nonneuronal cells

Gahring

Rogers

2005

AAPS J

135

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Expression and function of neuronal nicotinic ACh receptors in rat microvascular endothelial cells

Cited by 55 publications

References 28 publications

Nicotinic Enhancement of Proliferation in Bovine and Porcine Cerebral Microvascular Endothelial Cells

Nicotinic Enhancement of Proliferation in Bovine and Porcine Cerebral Microvascular Endothelial Cells

Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus

Neuronal nicotinic acetylcholine receptor expression and function on nonneuronal cells

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