Mechanisms of Vasorelaxation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72633/1/j.1527-3466.1992.tb00249.x.pd

Leukotrienes inhibit early stages of HIV-1 infection in monocyte-derived microglia-like cells

<p>Abstract</p> <p>Background</p> <p>Microglia are one of the main cell types to be productively infected by HIV-1 in the central nervous system (CNS). Leukotriene B₄(LTB₄) and cysteinyl-leukotrienes such as LTC₄are some of the proinflammatory molecules produced in infected individuals that contribute to neuroinflammation. We therefore sought to investigate the role of leukotrienes (LTs) in HIV-1 infection of microglial cells.</p> <p>Methods</p> <p>To evaluate the role of LTs on HIV-1 infection in the CNS, monocyte-derived microglial-like cells (MDMis) were utilized in this study. Leukotriene-treated MDMis were infected with either fully replicative brain-derived HIV-1 isolates (YU2) or R5-tropic luciferase-encoding particles in order to assess viral production and expression. The efficacy of various steps of the replication cycle was evaluated by means of p24 quantification by ELISA, luciferase activity determination and quantitative real-time polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>We report in this study that virus replication is reduced upon treatment of MDMis with LTB₄and LTC₄. Additional experiments indicate that these proinflammatory molecules alter the pH-independent entry and early post-fusion events of the viral life cycle. Indeed, LT treatment induced a diminution in integrated proviral DNA while reverse-transcribed viral products remained unaffected. Furthermore, decreased C-C chemokine receptor type 5 (CCR5) surface expression was observed in LT-treated MDMis. Finally, the effect of LTs on HIV-1 infection in MDMis appears to be mediated partly via a signal transduction pathway involving protein kinase C.</p> <p>Conclusions</p> <p>These data show for the first time that LTs influence microglial cell infection by HIV-1, and may be a factor in the control of viral load in the CNS.</p

Method for identifying ligands activating either excitatory or inhibitory G-protein-coupled receptors by functional coexpression in Xenopus oocytes

Xenopus oocytes devoid of their follicular enclosure provide a frequently used expression system for investigating receptors that transduce through activation of adenylyl cyclase following injection of the appropriate mRNA. However, due to a low basal activity of the cyclase they cannot be utilized to investigate receptor-mediated reductions in endogenous cAMP levels. In order to overcome this limitation, a model was designed in which test clones for such inhibitory receptors were co-expressed with a beta 2-adrenoceptor, which elevated cAMP upon exposure to isoproterenol. Following injection of mRNA to express the alpha 2 test receptor in the oocytes, marked reduction in cAMP could be measured after exposure to clonidine. Attenuation of cAMP levels was also seen following co-expression of the dopamine D2 receptor along with dopamine administration. Thus, after inducing a receptor-mediated tone in adenylyl cyclase activity, Xenopus oocytes can be conveniently used to study also ligands that bind to inhibitory G-protein coupled receptors

Involvement of local adrenergic receptors in the process of ovulation in gonadotrophin-primed immature rats

Immature female rats were primed with 4 i.u. PMSG at 08:00 h of Day 26. This results in ovulation in the morning of Day 29. The number of ovulations was counted in terms of newly formed corpora lutea in the morning of Day 30. Various adrenergic drugs were delivered into the ovarian bursa bilaterally in the afternoon of Day 27 to study their effect on ovulation. A methyl cellulose gel solution was used as vehicle to minimize leakage from the bursa. Noradrenaline, terbutaline and 4-aminopyridine significantly enhanced the number of corpora lutea compared to control ovaries injected with gel vehicle alone. The effect of terbutaline was counteracted by propranolol. Phentolamine partly blocked the noradrenaline-induced enhancement and the antagonist alone significantly reduced the number of ovulations. The results indicate that stimulation of alpha-adrenergic receptors (probably via actions in the follicle wall) as well as beta-receptors (influencing steroid-producing cells) may interfere with the ovulation process

Simultaneous and continuous measurement of choroid plexus blood flow and cerebrospinal fluid production: effects of vasoactive intestinal polypeptide

Using laser-Doppler flowmetry during ventriculocisternal perfusion with inulin-[14C]carboxylic acid, choroid plexus blood flow (CPBF) and CSF production were measured simultaneously in rats during periods of 3 h. Blood flow and CSF production decreased only slightly during control experiments. The effect of vasoactive intestinal polypeptide (VIP) was studied at different concentrations of the peptide given either intraventricularly or intravenously. Intraventricular administration of VIP (10(-9) or 10(-7) M) resulted in a decrease in CSF production of up to 30%, while CPBF increased by 20%, also demonstrating that CSF production and blood flow are not directly coupled in the choroid plexus. When infused intravenously, VIP (10 or 100 pmol/kg/min) increased CPBF, an effect partly antagonized at higher concentrations owing to a VIP-induced systemic hypotension. No effect of VIP on CSF production could be seen with intravenous administration

Intraovarian adrenergic nerves in the guinea-pig : development from fetal life to sexual maturity

The development of the intraovarian adrenergic nervous system was investigated in the guinea-pig by use of chemical determination of catecholamines with high performance liquid chromatography (HPLC) and with the formaldehyde-induced fluorescence method for visualization of adrenergic nerves (Falck-Hillarp technique). Ovaries from fetuses (39-40, 45-50, 55-57, 60-63 days of gestation) and young animals (1, 2, 3, 7, 14, 30, 40-45 days of age) were included in the study. The noradrenaline concentration was low in the ovaries from the youngest fetuses but increased with age, reaching a maximum level at 2 days post partum. A marked decrease in noradrenaline concentration from the second to the third day of life was found as a consequence of the rapid increase in the ovarian weight during this time. A similar decrease in ovarian noradrenaline concentration after a period of rapid ovarian growth was noted at 30 days of age. Measurable amounts of adrenaline were found in the ovary only in the fetal stages; the highest concentration (0.73 microgram) was detected at 55-57 days of gestation