Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor.
(1/373)
Nigrostriatal dopaminergic neurons undergo sprouting around the margins of a striatal wound. The mechanism of this periwound sprouting has been unclear. In this study, we have examined the role played by the macrophage and microglial response that follows striatal injury. Macrophages and activated microglia quickly accumulate after injury and reach their greatest numbers in the first week. Subsequently, the number of both cell types declines rapidly in the first month and thereafter more slowly. Macrophage numbers eventually cease to decline, and a sizable group of these cells remains at the wound site and forms a long-term, highly activated resident population. This population of macrophages expresses increasing amounts of glial cell line-derived neurotrophic factor mRNA with time. Brain-derived neurotrophic factor mRNA is also expressed in and around the wound site. Production of this factor is by both activated microglia and, to a lesser extent, macrophages. The production of these potent dopaminergic neurotrophic factors occurs in a similar spatial distribution to sprouting dopaminergic fibers. Moreover, dopamine transporter-positive dopaminergic neurites can be seen growing toward and embracing hemosiderin-filled wound macrophages. The dopaminergic sprouting that accompanies striatal injury thus appears to result from neurotrophic factor secretion by activated macrophages and microglia at the wound site. (+info)
Facilitatory beta2-adrenoceptors on cholinergic and adrenergic nerve endings of the guinea pig trachea.
(2/373)
Using electrical field stimulation of epithelium-denuded intact guinea pig tracheal tube preparations, we studied the presence and role of prejunctional beta2-adrenoceptors by measuring evoked endogenous acetylcholine (ACh) and norepinephrine (NE) release directly. Analysis of ACh and NE was through two HPLC systems with electrochemical detection. Electrical field stimulation (150 mA, 0.8 ms, 16 Hz, 5 min, biphasic pulses) released 29.1 +/- 2.5 pmol ACh/g tissue and 70.2 +/- 6.2 pmol NE/g tissue. Preincubation for 15 min with the selective beta2-adrenoceptor agonist fenoterol (1 microM) increased both ACh and NE overflow to 178 +/- 28 (P < 0.01) and 165 +/- 12% (P < 0.01), respectively, of control values, increases that were abolished completely by the selective beta2-adrenoceptor antagonist ICI-118551 (1 microM). Further experiments with increasing fenoterol concentrations (0.1-100 microM) and different preincubation periods (1, 5, and 15 min) showed a strong and concentration-dependent facilitation of NE release, with maximum response levels decreasing (from nearly 5-fold to only 2.5-fold of control value) with increasing agonist contact time. In contrast, sensitivity of facilitatory beta2-adrenoceptors on cholinergic nerves to fenoterol gradually increased when the incubation period was prolonged; in addition, a bell-shaped concentration-response relationship was found at 15 min of preincubation. Fenoterol concentration-response relationships (15-min agonist preincubation) in the presence of atropine and yohimbine (1 microM each) were similar in the case of NE release, but in the case of ACh release, the bell shape was lost. The results indicate a differential capacity and response time profile of facilitatory prejunctional beta2-adrenoceptors on adrenergic and cholinergic nerve terminals in the guinea pig trachea and suggest that the receptors on adrenergic nerves are more susceptible to desensitization. (+info)
Impact of development and chronic hypoxia on NE release from adrenergic nerves in sheep arteries.
(3/373)
To examine effects of development and chronic high-altitude hypoxia on sympathetic nerve function in sheep, norepinephrine release was measured in vitro from middle cerebral and facial arteries. Capsaicin was used to test the role of capsaicin-sensitive sensory nerves; norepinephrine release was not altered by capsaicin treatment. Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, decreased stimulation-evoked norepinephrine release in middle cerebral arteries from normoxic sheep with no effect in hypoxic arteries or facial arteries. Thus NO-releasing nerves augmented norepinephrine release. Furthermore, the function of NO-releasing nerves declined after chronic hypoxia. Despite loss of the augmenting effects of NO, stimulation-evoked fractional norepinephrine release was unchanged after chronic hypoxia, suggesting that middle cerebral arteries adapt to hypoxia by increasing stimulation-evoked norepinephrine release. In fetal facial arteries, chronic hypoxia resulted in a decline in stimulation-evoked norepinephrine release, but there was an increase in the adult facial artery. In the adult, adaptation to chronic hypoxia is similar in both cerebral and facial arteries. However, differential adaptation in fetal adrenergic nerves may reflect differences in fetal redistribution of blood flow in the face of chronic hypoxia but could also possibly contribute to increased incidence of fetal morbidity. (+info)
Estradiol modulates vascular response to melatonin in rat caudal artery.
(4/373)
The purpose of this study was to determine whether estrogen modulates the function of vascular melatonin receptors. We used the rat caudal artery and found that the contractile effects of melatonin were influenced by the estrous cycle, ovariectomy, and estrogen replacement. In arterial ring segments isolated from female rats, melatonin potentiated, in a concentration-dependent manner, contractions produced either by adrenergic nerve stimulation or by phenylephrine. Constrictor responses to melatonin were smaller in arteries from female rats in proestrus compared with other stages of the estrous cycle and after ovariectomy. Administration of 17beta-estradiol to ovariectomized female rats also resulted in decreased constriction of isolated arteries to melatonin; however, in vitro addition of 17beta-estradiol (10(-7) M) had no effect. In the caudal artery, melatonin appears to act on two receptor subtypes that mediate contraction and relaxation, respectively. The selective melatonin MT2-receptor antagonist 4-phenyl-2-propionamidotetraline (4P-PDOT) enhanced constrictor responses to melatonin in arterial segments from intact female rats, consistent with the inhibition of MT2 receptor-mediated relaxation. In contrast, 4P-PDOT had no significant effect in arteries from ovariectomized female rats. However, when estradiol was replaced in vivo, the effect of 4P-PDOT on melatonin responses was restored. Thus circulating estradiol appears to enhance MT2 melatonin-receptor function in the thermoregulatory caudal artery of the female rat resulting in increased vasodilatation in response to melatonin. (+info)
Adrenergic innervation in reactive human lymph nodes.
(5/373)
Several experimental models have demonstrated that the central nervous system is functionally linked to the immune system by means of the autonomic nervous system. Samples of 36 lymph nodes of patients whose ages ranged from 16 to 69 y were studied. In order to demonstrate the existence and distribution of sympathetic nerve fibres, a polyclonal antibody antityrosine hydroxylase (TH), with the streptavidin-biotin system of detection, was used. TH-positive nerve fibres appeared in all reactive patterns of the lymph nodes studied. Thin nerve fascicles ramified at the hilar region and also in the connective tissue septae. Adventitial adrenergic nerve fibres were found following afferent, and to a lesser extent, efferent blood vessels. Another source of incoming nerve fibres was found at capsular level, accompanying blood vessels. On the arterial side, the innervation ceased before reaching the follicular arterioles. Our demonstration of innervation in postcapillary venules could support a regulatory role of adrenergic neurotransmitters in lymphocyte traffic. Occasional nerve fibres were also seen in T areas among parenchymatous cells. These findings confirm the existence of sympathetic innervation in human lymph nodes, and provide indirect evidence that the psychoneuroimmune axis could also exist in humans. (+info)
Effects of prolonged cold storage on double peaked vasoconstrictor responses to periarterial nerve stimulation in isolated canine splenic arteries.
(6/373)
1. P2X-Purinoceptors and alpha1-adrenoceptors have previously been shown to involve in the double peaked vasoconstrictor responses to periarterial electrical nerve stimulation in the isolated and perfused canine splenic artery. The present study made an attempt to investigate effects of prolonged cold storage (7 days at 4 degrees C) on vasoconstrictor responses to periarterial electrical nerve stimulation, tyramine, noradrenaline and adenosine 5'-triphosphate (ATP) in the isolated canine splenic artery. 2. The periarterial nerve stimulation (1-10 Hz) readily causes a double peaked vasoconstriction in the non-stored preparations. After cold stored for 7 days, the double peaked vasoconstriction was still recognized, although the response became significantly smaller. The first phase was decreased relatively greater than the second phase by the cold storage. 3. In the cold stored preparations, the dose-response curve for tyramine was shifted to the right in a parallel manner. Prazosin almost completely inhibited tyramine-induced vasoconstriction but alpha,beta-methylene ATP failed to influence the response to tyramine. 4. The vasoconstrictor responses to noradrenaline and ATP were not significantly modified by the prolonged cold storage. 5. From these results, it is concluded that the functions of sympathetic co-transmission of purinergic components might be influenced more than that of adrenergic components in the cold storage canine splenic artery. (+info)
Role of protons in activation of cardiac sympathetic C-fibre afferents during ischaemia in cats.
(7/373)
1. Chest pain caused by myocardial ischaemia is mediated by cardiac sympathetic afferents. The mechanisms of activation of cardiac afferents during ischaemia remain poorly understood. Increased lactic acid production is associated closely with myocardial ischaemia. The present study examined the role of protons generated during ischaemia in activation of cardiac sympathetic C-fibre afferents. 2. Single-unit activity of cardiac afferents innervating both ventricles was recorded from the left sympathetic chain in anaesthetized cats. Epicardial tissue pH was measured within 1-1.5 mm of the surface by a pH-sensitive needle electrode. Responses of cardiac afferents to myocardial ischaemia, lactic acid, sodium lactate, acidic phosphate buffer and hypercapnia were determined. 3. Occlusion of the coronary artery for 5 min decreased epicardial tissue pH from 7.35 +/- 0.21 to 6.98 +/- 0.22 (P < 0.05). Epicardial placement of isotonic neutral phosphate buffer, but not saline, prevented the ischaemia-induced decrease in epicardial pH. This manoeuvre significantly attenuated the response of 16 afferents to 5 min of ischaemia (1.56 +/- 0.23 pre-treatment vs. 0.67 +/- 0.18 impulses s-1). Topical application of 10-100 microg ml-1 of lactic acid, but not sodium lactate, concentration-dependently stimulated 18 cardiac afferents. Inhalation with high-CO2 gas failed to activate 12 separate cardiac afferents. Furthermore, lactic acid stimulated cardiac afferents to a greater extent than acidic phosphate buffer solution, applied at a similar pH to the same afferents. 4. Collectively, this study provides important in vivo evidence that protons contribute to activation/sensitization of cardiac sympathetic C-fibre afferents during myocardial ischaemia. (+info)
5-Hydroxytryptamine(1A) receptor activation enhances norepinephrine release from nerves in the rabbit saphenous vein.
(8/373)
Although serotonergic receptor agonists are known to modulate release of central serotonin, less is known about the ability of serotonin to alter neurotransmission in peripheral adrenergic nerves. The present study used field stimulation (40V, 0.7 ms duration, 1-16 Hz) to contract the rabbit saphenous vein, an effect that was abolished in the presence of tetrodotoxin and prazosin (10(-6) M), consistent with stimulation of neuronal norepinephrine release. Furthermore, the field-stimulated contraction was not altered by the 5-hydroxytryptamine (5-HT)(1B/1D) receptor antagonist GR127935 (10(-6) M), but was markedly inhibited by the 5-HT(1A) receptor antagonist WAY 100635 (10(-6) M). GR127935 (10(-8) M) inhibited contraction to sumatriptan, documenting that the concentration used was sufficient to block 5-HT(1B/1D-like) vascular receptors in this tissue. Likewise, WAY 100635 (10(-6) M) inhibited contraction to the 5-HT(1A) receptor agonists (+/-)-8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT) and LY238729, without altering contraction to norepinephrine or sumatriptan. Furthermore, both 8-OH-DPAT and LY228729 enhanced the contractile response to field stimulation (1. 0-8.0 Hz) and activated norepinephrine release in the absence of field stimulation. Contractile responses of the rabbit saphenous vein to both 5-HT(1A) receptor agonists were markedly inhibited by prazosin and dextrally shifted by WAY 100635, supporting the idea that the 5-HT(1A) receptor agonists were activating presynaptic 5-HT(1A) receptors to enhance norepinephrine release even in the absence of field stimulation. Thus, in the rabbit saphenous vein, 5-HT(1A) but not 5-HT(1B/1D) receptors enhanced neurotransmitter release from adrenergic nerves. These observations suggested that serotonergic nerves or other cell types in the saphenous vein are activated by field stimulation to release serotonin, which in turn activates presynaptic 5-HT(1A) receptors on adrenergic neurons to effect norepinephrine release. To support this hypothesis, serotonin levels were measured in the saphenous vein and were increased after pargyline pretreatment (30 mg/kg s.c.), decreased after dl-p-chlorophenylalanine methyl ester pretreatment (300 mg/kg s.c.), and unaltered after pretreatment with 6-hydroxydopamine hydrobromide (100 mg/kg s.c.). Thus, we provide strong evidence for the 1) presence of serotonin and its direct synthesis independent of adrenergic nerves and 2) a novel excitatory effect of presynaptic 5-HT(1A) receptor activation on adrenergic nerves in a peripheral blood vessel. (+info)