Possible role of serotonin in Merkel-like basal cells of the taste buds of the frog, Rana nigromaculata. (1/1756)

Merkel-like basal cells in the taste buds of the frog were examined by fluorescence histochemistry, immunohistochemistry and electron microscopy. There were about 16-20 basal cells arranged in a radial fashion at the base of each taste bud. These cells were strongly immunopositive for serotonin antiserum. They were characterised by the presence of numerous dense-cored granules in the cytoplasm ranging from 80 to 120 nm in diameter, and of microvilli protruding from the cell surface. For 4 mo after sensory denervation by cutting the gustatory nerves, all cell types of the taste bud were well preserved and maintained their fine structure. Even at 4 mo after denervation, the basal cells exhibited a strong immunoreaction with serotonin antiserum. To investigate the function of serotonin in the basal cells in taste bud function, serotonin deficiency was induced by administration of p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, and of p-chloroamphetamine (PCA), a depletor of serotonin. After administration of these agents to normal and denervated frogs for 2 wk, a marked decrease, or complete absence, of immunoreactivity for serotonin was observed in the basal cells. Ultrastructurally, degenerative changes were observed in both types of frog; numerous lysosome-like myelin bodies were found in all cell types of the taste buds. The number of dense-cored granules in the basal cells also was greatly decreased by treatment with these drugs. Serotonin in Merkel-like basal cells appears to have a trophic role in maintenance of the morphological integrity of frog taste bud cells.  (+info)

Expression of Mash1 in basal cells of rat circumvallate taste buds is dependent upon gustatory innervation. (2/1756)

Mash1, a mammalian homologue of the Drosophila achaete-scute proneural gene complex, plays an essential role in differentiation of subsets of peripheral neurons. In this study, using RT-PCR and in situ RT-PCR, we investigated if Mash1 gene expression occurs in rat taste buds. Further, we examined dynamics of Mash1 expression in the process of degeneration and regeneration in denervated rat taste buds. In rat tongue epithelium, Mash1 gene expression is confined to circumvallate, foliate, and fungiform papilla epithelia that include taste buds. In taste buds, Mash1-expressing cells are round cells in the basal compartment. In contrast, the mature taste bud cells do not express the Mash1 gene. Denervation and regeneration experiments show that the expression of Mash1 requires gustatory innervation. We conclude that Mash1 is expressed in cells of the taste bud lineage, and that the expression of Mash1 in rat taste buds is dependent upon gustatory innervation.  (+info)

Effect of central corticotropin-releasing factor on carbon tetrachloride-induced acute liver injury in rats. (3/1756)

Central neuropeptides play important roles in many instances of physiological and pathophysiological regulation mediated through the autonomic nervous system. In regard to the hepatobiliary system, several neuropeptides act in the brain to regulate bile secretion, hepatic blood flow, and hepatic proliferation. Stressors and sympathetic nerve activation are reported to exacerbate experimental liver injury. Some stressors are known to stimulate corticotropin-releasing factor (CRF) synthesis in the central nervous system and induce activation of sympathetic nerves in animal models. The effect of intracisternal CRF on carbon tetrachloride (CCl4)-induced acute liver injury was examined in rats. Intracisternal injection of CRF dose dependently enhanced elevation of the serum alanine aminotransferase (ALT) level induced by CCl4. Elevations of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels by CCl4 were also enhanced by intracisternal CRF injection. Intracisternal injection of CRF also aggravated CCl4-induced hepatic histological changes. Intracisternal CRF injection alone did not modify the serum ALT level. Intravenous administration of CRF did not influence CCl4-induced acute liver injury. The aggravating effect of central CRF on CCl4-induced acute liver injury was abolished by denervation of hepatic plexus with phenol and by denervation of noradrenergic fibers with 6-hydroxydopamine treatment but not by hepatic branch vagotomy or atropine treatment. These results suggest that CRF acts in the brain to exacerbate acute liver injury through the sympathetic-noradrenergic pathways.  (+info)

Nitric oxide mediates sympathetic vasoconstriction at supraspinal, spinal, and synaptic levels. (4/1756)

The purposes of this study were to investigate the level of the sympathetic nervous system in which nitric oxide (NO) mediates regional sympathetic vasoconstriction and to determine whether neural mechanisms are involved in vasoconstriction after NO inhibition. Ganglionic blockade (hexamethonium), alpha1-receptor blockade (prazosin), and spinal section at T1 were used to study sympathetic involvement. NO was blocked with Nomega-nitro-L-arginine methyl ester (L-NAME). Regional blood flow in the mesenteric and renal arteries and terminal aorta was monitored by electromagnetic flowmetry in conscious rats. L-NAME (3-5 mg/kg iv) increased arterial pressure and peripheral resistance. Ganglionic blockade (25 mg/kg iv) significantly reduced the increase in resistance in the mesentery and kidney in intact and spinal-sectioned rats. Ganglionic blockade significantly decreased hindquarter resistance in intact rats but not in spinal-sectioned rats. Prazosin (200 micrograms/kg iv) significantly reduced the increased hindquarter resistance. We concluded that NO suppresses sympathetic vasoconstriction in the mesentery and kidney at the spinal level, whereas hindquarter tone is mediated at supraspinal and synaptic levels.  (+info)

Erythromycin enhances early postoperative contractility of the denervated whole stomach as an esophageal substitute. (5/1756)

OBJECTIVE: To determine whether early postoperative administration of erythromycin accelerates the spontaneous motor recovery process after elevation of the denervated whole stomach up to the neck. SUMMARY BACKGROUND DATA: Spontaneous motor recovery after gastric denervation is a slow process that progressively takes place over years. METHODS: Erythromycin was administered as follows: continuous intravenous (i.v.) perfusion until postoperative day 10 in ten whole stomach (WS) patients at a dose of either 1 g (n = 5) or 2 g (n = 5) per day; oral intake at a dose of 1 g/day during 1.5 to 8 months after surgery in 11 WS patients, followed in 7 of them by discontinuation of the drug during 2 to 4 weeks. Gastric motility was assessed with intraluminal perfused catheters in these 21 patients, in 23 WS patients not receiving erythromycin, and in 11 healthy volunteers. A motility index was established by dividing the sum of the areas under the curves of >9 mmHg contractions by the time of recording. RESULTS: The motility index after IV or oral administration of erythromycin at and after surgery was significantly higher than that without erythromycin (i.v., 1 g: p = 0.0090; i.v., 2 g: p = 0.0090; oral, 1 g: p = 0.0017). It was similar to that in healthy volunteers (i.v., 1 g: p = 0.2818; oral, 1 g: p = 0.7179) and to that in WS patients with >3 years of follow-up who never received erythromycin (i.v., 1 g: p = 0.2206; oral, 1 g: p = 0.8326). The motility index after discontinuation of the drug was similar or superior to that recorded under medication in four patients who did not experience any modification of their alimentary comfort, whereas it dropped dramatically parallel to deterioration of the alimentary comfort in three patients. CONCLUSIONS: Early postoperative contractility of the denervated whole stomach pulled up to the neck under either i.v. or oral erythromycin is similar to that recovered spontaneously beyond 3 years of follow-up. In some patients, this booster effect persists after discontinuation of the drug.  (+info)

Heterogeneous cardiac sympathetic denervation and decreased myocardial nerve growth factor in streptozotocin-induced diabetic rats: implications for cardiac sympathetic dysinnervation complicating diabetes. (6/1756)

Heterogeneous myocardial sympathetic denervation complicating diabetes has been invoked as a factor contributing to sudden unexplained cardiac death. In subjects with diabetic autonomic neuropathy (DAN), distal left ventricular (LV) denervation contrasts with preservation of islands of proximal innervation, which exhibit impaired vascular responsiveness. The aims of this study were to determine whether this heterogeneous pattern of myocardial sympathetic denervation occurs in a rat model of diabetes and to explore a potential association with regional fluctuations in myocardial nerve growth factor (NGF) protein. Myocardial sympathetic denervation was characterized scintigraphically using the sympathetic neurotransmitter analog C-11 hydroxyephedrine ([11C]HED) and compared with regional changes in myocardial NGF protein abundance and norepinephrine content after 6 and 9 months in nondiabetic (ND) and streptozotocin-induced diabetic (STZ-D) rats. In ND rats, no difference in [11C]HED retention or norepinephrine content was detected in the proximal versus distal myocardium. After 6 months, compared with ND rats, myocardial [11C]HED retention had declined in the proximal segments of STZ-D rats by only 9% (NS) compared with a 33% decrease in the distal myocardium (P < 0.05). Myocardial norepinephrine content was similar in both ND and STZ-D rats. At 6 months, LV myocardial NGF protein content in STZ-D rats decreased by 52% in the proximal myocardial segments (P < 0.01 vs. ND rats) and by 82% distally (P < 0.01 vs. ND rats, P < 0.05 vs. proximal segments). By 9 months, [11C]HED retention had declined in both the proximal and distal myocardial segments of the STZ-D rats by 42% (P < 0.01 vs. ND rats), and LV norepinephrine content and NGF protein were decreased in parallel. Therefore, 6 months of STZ-induced diabetes results in heterogeneous cardiac sympathetic denervation in the rat, with maximal denervation occurring distally, and is associated with a proximal-to-distal gradient of LV NGF protein depletion. It is tempting to speculate that regional fluctuations of NGF protein in the diabetic myocardium contribute to heterogeneous cardiac sympathetic denervation complicating diabetes.  (+info)

Hypoxia inhibits baroreflex vagal bradycardia via a central action in anaesthetized rats. (7/1756)

It is known that arterial baroreflexes are suppressed in stressful conditions. The present study was designed to determine whether and how hypoxia affects arterial baroreflexes, especially the heart rate component, baroreflex vagal bradycardia. In chloralose-urethane-anaesthetized rats, baroreflex vagal bradycardia was evoked by electrical stimulation of the aortic depressor nerve, and the effect of 15 s inhalation of hypoxic gas (4% O2) was studied. Inhalation of hypoxic gas was found to inhibit baroreflex vagal bradycardia. The inhibition persisted after bilateral transection of the carotid sinus nerve. Cervical vagus nerves were cut bilaterally and their peripheral cut ends were stimulated to provoke vagal bradycardia of peripheral origin so as to determine whether hypoxia could inhibit vagal bradycardia by acting on a peripheral site. In contrast to baroreflex vagal bradycardia, the vagus-induced bradycardia was not affected by hypoxic gas inhalation. It is concluded that baroreflex vagal bradycardia is inhibited by hypoxia and the inhibition is largely mediated by its direct central action.  (+info)

A substituted dextran enhances muscle fiber survival and regeneration in ischemic and denervated rat EDL muscle. (8/1756)

Ischemia and denervation of EDL muscle of adult rat induce a large central zone of degeneration surrounded by a thin zone of peripheral surviving muscle fibers. Muscle regeneration is a complex phenomenon in which many agents interact, such as growth factors and heparan sulfate components of the extracellular matrix. We have shown that synthetic polymers, called RGTA (as regenerating agents), which imitate the heparan sulfates, are able to stimulate tissue repair when applied at the site of injury. In crushed muscles, RGTA were found to accelerate both regeneration and reinnervation. In vitro, RGTA act as protectors and potentiators of various heparin binding growth factors (HBGF). It was postulated that in vivo their tissue repair properties were due in part to an increase of bioavailability of endogenously released HBGF. In the present work, we show that ischemic and denervated EDL muscle treated by a unique injection of RGTA differs from the control after 1 wk in several aspects: 1) the epimysial postinflammatory reaction is inhibited and the area of fibrotic tissue among fibers is reduced; 2) the peripheral zone, as measured by the number of intact muscle fibers, was increased by more than twofold; and 3) In the central zone, RGTA enhances the regeneration of the muscle fibers as well as muscle revascularization. These results suggest that RGTA both protects muscle fibers from degeneration and preserves the differentiated state of the surviving fibers. For the first time it is demonstrated that a functionalized polymeric compound can prevent some of the damage resulting from muscle ischemia. RGTA may therefore open a new therapeutic approach for muscle fibrosis and other postischemic muscle pathologies.  (+info)