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

Embryonic striatal grafts develop a modular organization in which patches of tissue enriched in many transmitter substances characteristic of striatum (P regions) are embedded in surrounds (NP regions) expressing only low levels of these substances. Catecholaminergic fibers from the host brain, identified by their expression of tyrosine hydroxylase (TH), grow into such grafts and selectively terminate in the striatum-like P regions. This terminal pattern suggests that cell-cell affinities between neurons of the substantia nigra and striatum may play a role either in the aggregation of the striatal cells into P regions, or in the targeting of the TH-positive fibers to the cell clusters. In the present study, we tested the first of these possibilities. Striatal grafts derived from embryonic day 15 striatal primordia were implanted into the ibotenate-damaged host striatum of rats previously treated with 6-hydroxydopamine (6-OHDA) to destroy TH-containing dopaminergic nigrostriatal afferents. The 6-OHDA lesions that eliminated nearly all TH-like immunostaining in the host striatum also resulted in disappearance of nearly all TH-positive fibers in the grafts. In this dopamine-depleted environment, the grafts nevertheless developed a clear modular organization. They contained striatum-like patches with neurons expressing many of the neurochemicals characteristic of striatum (ACh, ChAT, calbindin-D28KD, met-enkephalin, and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein-32,000 or DARPP-32), and these patches were surrounded by graft tissue expressing few of these striatal markers. These observations suggest that the ingrowth of TH-positive fibers from the host is not obligatory for the sorting out of striatal from nonstriatal cells during the formation of P regions in embryonic striatal grafts. Despite the fact that dopaminergic denervation of the host striatum did not disrupt either the aggregation of grafted cells into P regions or the acquisition of striatal neurochemical phenotypes by cells in the P regions, there were clear differences between the staining patterns of these grafts and grafts placed into dopamine-innervated striatum. Most striking was a sharp increase of met-enkephalin-like immunostaining in the P zones of the denervated grafts. Upregulation of met-enkephalin is known to occur in the dopamine-depleted mature striatum, and was observed in the parts of host striatum surrounding the grafts on the side ipsilateral to the 6-OHDA lesions. This result suggests that functional interactions between dopaminergic and enkephalinergic systems can occur in the striatal circuits reconstructed by embryonic striatal grafting. More generally, our results suggest that TH-containing afferents from the host striatum, though not required for induction and maintenance of striatal phenotypy in striatal grafts, can chronically regulate neurotransmitter/neuromodulator expression in neurons of the striatum-like P zones in a manner similar to that found for the normal striatum.
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PMID:Influence of mesostriatal afferents on the development and transmitter regulation of intrastriatal grafts derived from embryonic striatal primordia. 127 38

The effects of the putative neurotransmitters acetylcholine, adrenaline, adenosine, ATP, bombesin, 5-hydroxytryptamine, met-enkephalin, neurotensin, somatostatin, substance P and VIP have been investigated in the perfused intestine of the cod, Gadus morhua. The presence and distribution of the different types of nerves was investigated with immunohistochemistry and Falck-Hillarp fluorescence histochemistry. A spontaneous rhythmic activity of the perfused preparations usually occurred within a few minutes from the start of the experiment. This activity was diminished or abolished by addition of atropine, methysergide or tetrodotoxin to the perfusion fluid. Acetylcholine, 5-hydroxytryptamine or substance P caused a contraction of the intestinal wall. The response to acetylcholine was blocked by atropine but not by tetrodotoxin, while the response to 5-hydroxytryptamine was blocked by methysergide and usually also by tetrodotoxin. This indicates that the effect of acetylcholine is direct on the muscle cells, while the effect of 5-hydroxytryptamine may be at least partly via a second neuron. All adrenergic agonists (adrenaline, isoprenaline and phenylephrine) had a dominating inhibitory effect on the intestine. Experiments with antagonists showed that the inhibition is due to stimulation of both alpha-adrenoceptors and beta-adrenoceptors. ATP, adenosine and somatostatin also caused a relaxation of the intestinal wall, often followed by a contraction. Met-enkephalin produced variable responses, either a relaxation, a contraction or both. Bombesin caused a weak inhibition, if anything. Neurotensin and VIP did not visibly affect the intestinal motility. 5-HT-, substance P- and VIP-like immunoreactivity and catecholamine fluorescence were observed in the myenteric plexus, submucosa and muscle layers in all parts of the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurotransmitters in the intestine of the Atlantic cod, Gadus morhua. 241 59

Intracellular recordings from primary mechanosensory neurones (dorsal cells) in the lamprey spinal cord were used to test the membrane effects of a variety of putative neuromodulatory agents. gamma-Aminobutyric acid (GABA) produced a dose-dependent increase in the duration of mixed Na-Ca or pure Ca action potentials in these cells. L-Glutamate and glycine produced minimal broadening of Ca action potentials. Acetylcholine, noradrenaline, serotonin, met-enkephalin, D-glutamate and dopamine had no effect. The pharmacology of GABA's action appeared to be complex. While the GABAA receptor antagonists, bicuculline, picrotoxin and curare, did not block GABA's effect, both the GABAA receptor agonist, muscimol, and the GABAB-receptor agonist, baclofen, occasionally broadened Ca action potentials in these cells. GABA had no effect on the resting potential, passive current-voltage (I-V) characteristics and pure Na action potential of dorsal cells, ruling out an action on passive membrane channels, transmitter-activated channels, or on those voltage-dependent channels activated during the Na action potential. Thus, GABA affected dorsal cells only when a significant Ca current was evident. GABA appeared not to increase the conductance of the Ca channels since its action was accompanied by an increase in input resistance, suggesting an inhibition of Ca-dependent conductance that normally acts to repolarize the membrane during a Ca action potential. An inhibitory effect of GABA on a Ca-dependent Cl conductance was ruled out in experiments where the Cl gradient was altered by removal of extracellular Cl without affecting GABA-induced Ca action potential prolongation. Dorsal cells have a prominent Ca-dependent K conductance (gK(Ca], and it is this conductance that GABA may inhibit. Consistent with this was the observation that the hyperpolarizing after-potential that follows Ca action potentials in dorsal cells, which reflects gK(Ca) in these cells and whose duration is normally increased when the Ca action potential duration increases, was not prolonged when the Ca action potential was broadened by GABA. Further, the failure of GABA to prolong Ba action potentials was consistent with this proposed mechanism of action, since Ba apparently does not activate gK(Ca) in these cells. Forskolin, a specific adenylate cyclase activator, caused broadening of Ca action potentials in lamprey dorsal cells comparable in magnitude to that of GABA. Thus, an increase in intracellular cyclic AMP is a candidate for the intracellular mediator of GABA's effect on these cells.
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PMID:Prolongation of calcium action potentials by gamma-aminobutyric acid in primary sensory neurones of lamprey. 243 26

Somatostatin, morphine, and opioids inhibit transmitter release at intact neuromuscular junctions between ciliary ganglion neurons and the choroidal smooth muscle of the chick eye. Somatostatin and morphine, however, have no effect on release from terminals on the striated muscle target of the ciliary ganglion, the iris. In neuronal terminals of both the choroid and the iris, a high-affinity Na+-dependent choline uptake-mediated ACh synthesis is present at hatching. Both tissues exhibit a basal release of 3H-ACh which is potentiated severalfold during a 5 minute incubation in 55 mM K+ Tyrodes. Fifty percent of the basal release and 100% of the stimulated release are Ca2+ dependent and probably mediated through N-like voltage-dependent Ca2+ channels. Co-incubation of the choroid with 10 microM morphine sulfate blocks approximately 90% of the stimulated release. The same effect is seen with 100 nM somatostatin, 10 microM dynorphin, and 100 microM met-enkephalin arginine phenylalanine. Preincubation of the excised choroid with pertussis toxin (200 ng/ml) reverses the inhibitory effects of both morphine and somatostatin. In contrast, 3H-ACh release from terminals in the striated iris is not affected by either morphine or somatostatin at micromolar levels. These results suggest that both opiate and somatostatin receptors are present in the choroid target and that they may act through a final common pathway to modulate ACh release via G proteins. Second messengers such as cyclic AMP or diacylglycerol do not appear to mediate these effects; neither increasing cAMP levels in terminals nor activation of protein kinase C affects evoked release or its inhibition by morphine or other neuromodulators. It is unclear whether endogenous neuromodulation occurs in this system, although somatostatin-like immunoreactivity can be demonstrated in terminals of choroid neurons.
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PMID:Opiate and peptide inhibition of transmitter release in parasympathetic nerve terminals. 256 61

In summary, 5HT, ACh, NE, E and DA appear to stimulate hypothalamic CRH secretion whereas activation of the GABA/BZD system seems to decrease the responsivity of the CRH neuron to stimulatory neurotransmitters (Fig. 6). Hypothalamic CRH released from the hypothalamic neuron not only activates the HPA axis, but also stimulates the locus coeruleus-norepinephrine system (LC) and the central sympathetic system (CSS). CRH also induces secretion of hypothalamic POMC gene-derived peptides, such as ACTH, beta-EP, alpha-MSH and CLIP. These peptides as well as CRH itself, decrease the responsivity of the CRH neuron to stimulatory inputs. In addition, glucocorticoids restrain the activity of both the CRH neuron and the locus coeruleus and may also inhibit the secretion of POMC gene-derived peptides by the POMC neurons of the arcuate nucleus. Hypothalamic CRH secretion is regulated also by a number of mediators of the immune response, such as IL-1, IL-2, TNF-alpha and PGF2 alpha, PAF and EGF. Although the physiologic significance of this regulation is largely unknown, it is tempting to speculate that cytokines and mediators of inflammation released in vivo may activate the HPA axis to trigger a glucocorticoid-mediated counter-regulatory mechanism to restrain the immune system (Fig. 7). (Formula: see text). Fig. 7. Schematic representation of the interactions between the HPA axis and the immune system. Continuous lines represent stimulatory inputs and interrupted lines represent inhibitory inputs. In conclusion, our in vitro hypothalamic organ culture system allowed us to examine the regulation of CRH secretion in a direct and specific manner. Some of our observations may help with better understanding of the role played by CRH in the complex symptomatology of stress. In making extrapolations and interpretations from the in vitro data, however, we should try to keep in mind the words of Claude Bernard, "... If we break up a living organism by isolating its different parts it is only for the sake of ease in analysis and by no means in order to consider them separately. Indeed when we wish to ascribe to a physiological quality its value and true significance we must always refer it to this whole and draw our final conclusions only in relation to the effects in the whole".
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PMID:Regulation of rat hypothalamic corticotropin-releasing hormone secretion in vitro: potential clinical implications. 290 18

Single and combined effects of intracerebroventricular bolus injection of Ang. II (200 ng), ACh (6 micrograms) and met-enkephalin (50 micrograms) on mean arterial pressure (MAP), was tested in Sprague-Dawley albino rats. A metallic cannula was implanted in the third ventricle according to standard stereotaxic procedures under pentobarbital anesthesia (35 mg/kg). On the third day, the animal was anesthetized again, a carotid artery was cannulated and connected to a pressure transducer for recording of MAP. Ang. II increased MAP; ACh produced a significant increase in the initial 5 minutes after injection and met-enkephalin did not induce any significant changes in MAP. The combined effect showed interesting results. Instead of a potentiation of the rise in MAP, Ang. II and ACh, when given together, did not show any significant changes. Also, met-enkephalin blocked the hypertensive response due to Ang. II, if given combined. This is compatible with an inhibitory action of met-enkephalin on an angiotensinergic neuronal system. A simplified hypothetical model that explains the findings described above is proposed as a working hypothesis.
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PMID:[Combined effect of intracerebroventricular injections of angiotensin II, met-enkephalin and acetylcholine on mean arterial pressure in albino rats]. 320 98

The present experiments show the presence of both metenkephalin-like and met-enkephalin-Arg6-Phe7-like immunoreactivity in the superior cervical ganglion of the cat; this was determined by radioimmunoassay after high-pressure liquid chromatography separation of tissue extracts. There was measurable efflux of both peptides, as determined by radioimmunoassay of ganglionic perfusates; this measure was increased by thiorphan, an enkephalinase inhibitor. The effect of the 2 peptides on ACh release was determined: The stable analog of methionine-enkephalin, D-Ala2-methionine-enkephalinamide, did not affect ACh release from the ganglion; in contrast, methionine-enkephalin-Arg6-Phe7 significantly depressed evoked ACh release. The effect of met-enkephalin-Arg6-Phe7 to decrease ACh release was antagonized, although only partially, by the opioid antagonist naloxone. Thus, it appears that methionine-enkephalin-Arg6-Phe7 alters ACh release from the superior cervical ganglion by acting, at least in part, on a presynaptic opioid receptor. The results suggest that in the cat superior cervical ganglion, the heptapeptide enkephalin might have a significant role in the regulation of synaptic transmission, which is unrelated to its potential function as a precursor for methionine-enkephalin.
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PMID:Effect of endogenous opioid peptides on acetylcholine release from the cat superior cervical ganglion: selective effect of a heptapeptide. 359 43

This paper presents a quantitative and sensitive assay for the measurement of chemosensory behavior in Tetrahymena. The two-phase assay is easy to perform in large quantities, so a variety of compounds can be screened under comparable conditions. A suspension of 2 x 10(5) cells ml-1 (the upper phase) is starved for 20-40 h and then gently placed on top of a 5% solution of Metrizamide (the lower phase) in a disposable microcuvette. The optical density of the lower phase is monitored at 600 nm with an automated spectrophotometer at selected time points. Optimum sensitivity of the assay is achieved when the cells slowly but continuously enter the lower phase, so that about 5% of them will be in the lower phase within 30 min. Optimal chemosensory responses occurred in Tetrahymena thermophila at about 25 degrees C. The response was delayed at 15 degrees C and markedly reduced at 35 degrees C. The data suggest three bases for quantifying the response in the assay: (1) initial slope of the absorbance versus time; (2) final maximal absorbance within the time period of measurement; and (3) signal-to-noise ratio (S/N) at a fixed time. We have quantified--in terms of S/N--the chemosensory responses in Tetrahymena for the following compounds: beta-endorphin, fibroblast growth factor, insulin, and platelet-derived growth factor (PDGF); these substances were active in nanomolar concentrations, and the maximal S/N was between 3 and 5.1. Acetylcholine was active only in millimolar concentrations; maximal S/N was 4.1 at 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An improved quantitative assay for chemokinesis in Tetrahymena. 791 98

In addition to the magnocellular hypothalamic nuclei, arginine vasopressin (AVP)-containing neurons have also been identified in limbic structures, including the hippocampus and amygdala. In the present study, we compared the qualitative properties of the in vitro release of AVP from the dissected hypothalamus with the in vitro release from the dissected amygdala and used these release systems to evaluate the interactions with neurotransmitters and cytokines. The areas of the paraventricular nucleus and supraoptic nucleus that contain the AVP neurons and that receive cholinergic innervation are also interleukin (IL)-1 beta immunoreactive. Acetylcholine or high KCl (60 mM) induces AVP release in both regions, and the AVP release is calcium dependent. Acetylcholine-induced AVP release is antagonized by atropine or mecamylamine, indicating that both muscarinic and nicotinic receptors are mediating the cholinergic effect in these brain regions. IL-1 beta (100 U/ml) had no effect on the basal AVP release from the hypothalamus, but significantly potentiated the acetylcholine-induced AVP release, lowering the threshold from 500 to 100 nM. This effect was completely blocked in the presence of neutralizing antibodies to IL-1 beta, atropine (10 microM) or mecamylamine (10 microM). IL-6, like IL-1 beta, also potentiated acetylcholine-induced AVP release, but to a lesser extent. Neither tumor necrosis factor-alpha nor interferon-gamma had any effect on the basal or acetylcholine-induced AVP release from the hypothalamus. None of the cytokines tested had any effect on the basal or acetylcholine-induced AVP release from the amygdala. Our results suggest a hypothalamic site of action of IL-1 beta and IL-6 on the acetylcholine-induced AVP release. The stimulatory effects of IL-1 and IL-6 on adrenocorticotropin release have been ascribed to an increased release of corticotropin-releasing factor (CRF). These data further suggest that, in addition to CRF, AVP plays a role in the bidirectional communication between neuroendoc ine and immune systems. Understanding the mode of interaction between IL-1 beta and IL-6 with AVP could clarify pathophysiologic or toxic effects of high brain levels of these cytokines.
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PMID:IL-1 beta potentiates the acetylcholine-induced release of vasopressin from the hypothalamus in vitro, but not from the amygdala. 815 70

This review is concerned with recent literature on the neural control of the pituitary pars intermedia of the amphibian Xenopus laevis. This aquatic toad adapts skin colour to the light intensity of its environment, by releasing the proopiomelanocortin (POMC)-derived peptide alpha-MSH (alpha-melanophore-stimulating hormone) from melanotrope cells. The activity of these cells is controlled by brain centers of which the hypothalamic suprachiasmatic and magnocellular nuclei, respectively, inhibit and stimulate both biosynthesis and release of alpha-MSH. The suprachiasmatic nucleus secretes dopamine, GABA, and NPY from synaptic terminals on the melanotropes. The structure of the synapses depends on the adaptation state of the animal. The inhibitory transmitters act via cAMP. Under inhibition conditions, melanotropes actively export cAMP, which might have a first messenger action. The magnocellular nucleus produces CRH and TRH. CRH, acting via cAMP, and TRH stimulate POMC-biosynthesis and POMC-peptide release. ACh is produced by the melanotrope cell and acts in an autoexcitatory feedback on melanotrope M1 muscarinic receptors to activate secretory activity. POMC-peptide secretion is driven by oscillations of the [Ca2+]i, which are initiated by receptor-mediated stimulation of Ca2+ influx via N-type calcium channels. The hypothalamic neurotransmitters and ACh control Ca2+ oscillatory activity. The structural and functional aspects of the various neural and endocrine steps in the regulation of skin colour adaptation by Xenopus reveal a high degree of plasticity, enabling the animal to respond optimally to the external demands for physiological adaptation.
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PMID:Background adaptation by Xenopus laevis: a model for studying neuronal information processing in the pituitary pars intermedia. 940 33


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