Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper discusses the current evidence supporting the notion that endogenous carbon monoxide (CO) is a modulator of neuroendocrine function. CO is normally formed in the body during the enzymatic catabolism of heme moieties by heme oxygenase (HO). Three HO isoforms have been described to date: HO-1, HO-2 and HO-3. In the brain, CO is principally generated by HO-2 but, in discrete brain areas such as the paraventricular nuclei of the hypothalamus, a role for HO-1 is also possible. Moreover, under pathological conditions, the latter isoform is expressed by activated glial cells. The possible contribution by the recently described HO-3 remains to be established. Once formed, CO exerts its biological effects mainly via the activation of soluble guanylyl cyclase, but alternative signaling mechanisms, such as the activation of cyclooxygenase or the inhibition of cytochrome P450, have also been reported. In in vitro studies, the formation of CO within the hypothalamus has been associated with inhibition of the release of hormones such as corticotropin-releasing hormone, arginine vasopressin and oxytocin involved in hypothalamo-pituitary-adrenal axis activation and, conversely, with stimulation of luteinising hormone-releasing hormone release, thus suggesting that the gas may have a neuroendocrine role which may be to prevent over-exuberant activation of the hypothalamo-pituitary-adrenal axis and inhibition of reproductive processes within the hypothalamus during stress. At present, however, the possible pathophysiological relevance of the in vitro observations remains to be demonstrated.
 ...
PMID:The role of carbon monoxide in the regulation of neuroendocrine function. 965 Aug 14

Striated muscle of the esophagus was until recently considered to consist of "classical" skeletal muscle fibers innervated by cholinergic vagal motoneurons. The recently described co-innervation originating from enteric neurons expressing nNOS, VIP, NPY, and galanin added a new dimension of complexity. The aim of this study was to summarize current knowledge about, and to get further hints as to the possible function of enteric co-innervation of striated esophageal muscle fibers. Aldehyde fixed rat esophagi were processed for immunocytochemistry for CGRP or VAChT (to demonstrate vagal motor terminals), nNOS/NADPH-d, VIP, NPY, and galanin (to demonstrate enteric terminals), met-enkephalin, mu opiate receptor, muscarinic receptors m1-3, soluble guanylyl cyclase, and cGMP dependent kinase type I and II. Motor endplates were visualized using fluorochrome tagged alpha-bungarotoxin to label nicotinic receptors, or with AChE histochemistry. Besides light and confocal laser scanning microscopy, immuno electron microscopy was also employed. Up to 80% of motor endplates were co-innervated. In addition to nNOS, VIP, NPY, and galanin, many enteric terminals in esophageal motor endplates expressed met-enkephalin. Some appeared to stain for the muscarinic m(2) receptor. There was prominent immunostaining for the micro opioid receptor in the sarcolemma at both junctional and extrajunctional sites. Immunostaining for soluble guanylyl cyclase was prominent immediately beneath the clusters of nicotinic receptors. Enteric varicosities and vagal terminals intermingled in motor endplates often without intervening teloglial processes. During ontogeny, initially high co-innervation rates were reduced to adult levels in a cranio-caudally progressing manner. We conclude that, in addition to a possible nitrergic, VIP-, NPY-, and galaninergic modulation of neuromuscular transmission by enteric neurons, opioidergic mechanisms could play a role. On the other hand, cholinergic influence on enteric neurons may be exerted also by the nucleus ambiguus via motor endplates, in addition to the input from the dorsal motor nucleus. The observations that enteric nerve fibers contact striated muscle fibers at specialized sites, i.e., motor endplates, and that these contacts appear in an ordered cranio-caudal sequence after cholinergic motor endplates have been established point to a specific function in neuronal control of esophageal muscle rather than to be an unspecific "hangover" from the smooth muscle past of this organ.
 ...
PMID:Enteric co-innervation of striated muscle fibers in the esophagus: just a "hangover"? 1114 27

The gaseous radical nitric oxide (NO) is catalyzed by conversion of L-arginine to L-citrulline by one cytokine inducible form (iNOS), which becomes active only within hours after the inducing event, and by two constitutively expressed forms, endothelial (eNOS) and neuronal (nNOS), which are regulated by the cytosolic concentration of free Ca2+. Brain nNOS is physiologically present in discrete populations of neurons, which are all excited by glutamate via the ionotropic N-methyl-D-aspartate (NMDA) receptor, which controls a Ca2+ channel. After its diffusion into the extraneuronal space, NO may activate in neurons, which as a rule do not stain for NOS, soluble guanylyl cyclase and formation of cGMP as an intracellular messenger. Beyond that, NO is important as a feedback regulator of glutamatergic excitation. NO as a nitrosylating agent enhances disulfide bonding of vicinal sulfhydryl (thiol) groups of the redox modulatory site of the NMDA receptor complex and thereby down-regulates its Ca2+ channel activity. Histochemical studies have revealed the presence of a large number of NOS containing neurons in the magnocellular and parvocellular subdivisions of hypothalamic nuclei. Numerous studies conform to the view that NO participates in the control of many different neurosecretory processes, especially of the corticotropin-releasing hormone (CRH) neurosecretory system. The redox-modulatory site of the NMDA receptor appears, therefore, as a critical structure in the control of the hypothalamic-pituitary-adrenocortical (HPA) axis. Moreover, glucocorticoids augment neuronal excitotoxicity by increasing the expression of glutamate receptors and inhibition of glutamate reuptake. In attempting to explain the many conflicting results obtained in studies with NO, it may be worthwhile to consider that the actual redox-environment of distinct loci of the brain may determine the final function of NO, acting either as a transmitter or neuromodulator or, in the worst case, causing neurodestruction. It seems likely that any kind of stress by altering the ratio of reduced vs oxidized thiols within the central nervous system influences neuronal excitability, with NO working either as an amplifier or as a feedback regulator of neuronal excitation or inhibition, which may alter acutely or chronically, among others, the homeostasis of a given neurosecretory system.
 ...
PMID:Role of nitric oxide in the control of the hypothalamic-pituitary-adrenocortical axis. 1115 2

Heme oxygenase (HO) cleaves the tetrapyrrolic ring of cellular heme moieties liberating carbon monoxide (CO) and equimolar amounts of free iron and biliverdin (BV). BV is in turn converted into bilirubin (BR) by the cytosolic enzyme BV reductase. Three HO isoforms have been described to date: HO-1, HO-2, and HO-3. All these isoforms are present in nervous tissue with different localizations and regulation. CO, the gaseous product of HO, exerts its biological effects through the activation of soluble guanylyl cyclase, but alternative signaling pathways, such as the activation of cyclooxygenase, have also been reported in the brain. In vitro and in vivo studies showed that CO, at the hypothalamic level, plays a key role in the modulation of stress response because it inhibits the release of antiinflammatory neuropeptides, such as corticotropin-releasing hormone and arginine vasopressin, and increases body temperature in rodents exposed to psychological stressors (stress fever). In the last few years, a new role of BR as an endogenously produced antioxidant has emerged, and several reports have shown that BR contributes to prevent cell damage mediated by reactive oxygen species, as well as nitric oxide and its congeners.
 ...
PMID:Heme oxygenase and its products in the nervous system. 1534 48