Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The facilitatory effect of intrathecal (i.t.) morphine on the excitability of the nociceptive flexor reflex was examined in decerebrate, spinalized, unanesthetized rats with intact or sectioned sciatic nerves. Low doses of i.t. morphine (10 ng in rats with intact nerves and 10 or 100 ng in rats with sectioned nerves) facilitated the flexor reflex. Higher doses of morphine caused facilitation followed by reflex depression. Facilitation of the flexor reflex induced by 10 or 100 ng morphine was prevented by i.t. naloxone (1 microgram). In rats with intact sciatic nerves the facilitation was partially antagonized by the tachykinin antagonist spantide II (D-NicLys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nle 11)-substance P (SP), indicating that the reflex facilitation evoked by low doses of morphine may be due to the release of SP and perhaps other neuropeptides. In axotomized animals, 14-20 days after unilateral sciatic nerve section, spantide II failed to antagonize morphine-induced facilitation, suggesting that SP or other tachykinins, no longer played a role in this effect. In contrast, the vasoactive intestinal peptide (VIP) antagonist (N-Ac-Tyr1,D-Phe2)-GRF (1-29)-NH2 blocked morphine-induced reflex facilitation in axotomized rats, but not in rats with intact nerves. The present study provides evidence that low doses of morphine may induce the release of excitatory neuropeptides, thereby facilitating spinal nociceptive transmission. The identity of the neuropeptides depends on whether or not peripheral axons are intact, tachykinins in rats with intact nerves and VIP in axotomized rats.
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PMID:Low-dose intrathecal morphine facilitates the spinal flexor reflex by releasing different neuropeptides in rats with intact and sectioned peripheral nerves. 171 3

This study tests the hypothesis that atrial natriuretic factor (ANF) and C-ANF(4-23)-NH2 (C-ANF) augment cGMP generation and inhibit both cAMP generation and depolarization-induced catecholamine release in nerve growth factor treated pheochromocytoma cells by a pertussis toxin (PTX)-sensitive mechanism. Synthetic rat ANF(99-126) and the clearance receptor antagonist C-ANF (10(-12)-10(-9) M) inhibited basal and 5 microM vasoactive intestinal peptide (VIP)-induced cAMP generation in a concentration-dependent manner. These actions of ANF and C-ANF were blocked by 12-18 h pretreatment with PTX (100 ng/ml), suggesting ANF receptor coupling to adenylate cyclase via an inhibitory guanine nucleotide-binding protein. Both ANF (10(-11)-10(-9) M) and C-ANF (10(-11)-10(-8) M) also inhibited K(+)-induced catecholamine release in a concentration-dependent manner. ANF (10(-11)-10(-8) M) increased cGMP generation in a concentration-dependent manner but C-ANF did not. The accumulation of cGMP in response to ANF was not altered by treatment with PTX. Therefore, PTX dissociated the increased concentrations of cGMP from the ANF-mediated depression of evoked catecholamine release. C-ANF also dissociated elevations in cGMP concentrations from an ANF-mediated attenuation of evoked catecholamine release. The results of this study indicate that ANF inhibits adrenergic neurotransmission independent of guanylate cyclase.
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PMID:Neuromodulatory effects of atrial natriuretic factor are independent of guanylate cyclase in adrenergic neuronal pheochromocytoma cells. 197 29

We recently reported that acute pharmacologic depression of dopaminergic tone at different times of day unmasks a sex-specific endogenous stimulatory rhythm regulating PRL secretion. The PRL secretory responses of ovariectomized rats to the dopamine antagonist domperidone (DOM) were higher at 0300 and 1700 h than at 1200 h. These are the times during which surges of PRL appear in mated rats. This experimental paradigm was used to investigate the roles of the putative PRL-releasing factors (PRFs) oxytocin (OT), vasoactive intestinal peptide (VIP), and serotonin (5-HT) in this rhythm. The role of OT was studied by infusion of the OT antagonist 1-deamino-2-D-Trp-4-Val-8-Orn-Oxytocin (OT-A, 0.5 microgram/kg min) for 6 h. Two hours after beginning the OT-A infusion DOM was administered, as a single injection of 200 micrograms/kg iv at either 0300, 1200, or 1700 h. Serial blood samples were collected immediately before and 5, 10, 20, 30, 60, 120, 180, and 240 min after DOM administration. Infusion of OT-A attenuated the heightened PRL secretory responses to DOM given at both 0300 and 1700 h but did not affect the response at 1200 h. The role of VIP was studied by infusing the VIP antagonist [D, 4-Cl-Phe6,Leu17] VIP (VIP-A, 0.1 microgram/kg.min) as described above. VIP-A infusion had no effect on the PRL secretory responses to DOM given at 1200 or 1700 h but attenuated the heightened response at 0300 h. In order to study the role of 5-HT in the rhythm, rats were pretreated with p-chlorophenylalanine (250 mg/kg sc) 48 and again 24 h before the experiment. Pretreatment with p-chlorophenylalanine had no effect on the PRL secretory responses to DOM given at 0300 or 1200 h, but it attenuated the augmented PRL secretory response at 1700 h. These data suggest that both VIP and OT act as endogenous PRFs at 0300 h and 5-HT and OT act as PRFs at 1700 h. We propose that VIP and 5-HT are continuously active oscillatory neurotransmitters regulating OT release into pituitary portal blood and that these daily events only eventuate in PRL release when the mating stimulus has release the lactotroph from the inhibitory effects of dopamine.
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PMID:Hypothalamic factors involved in the endogenous stimulatory rhythm regulating prolactin secretion. 252 68

The effects of a number of vasoactive and neurotransmitter substances on lymphocyte traffic were studied by assessing their effects on the release of lymphocytes into primary peripheral (popliteal) nodal efferent lymph of sheep following acute infusion into cannulated afferent nodal lymphatics. In a total of 23 experiments, the output of lymphocytes, small and blast, was increased by serotonin, substance P, bombesin, [met]enkephalin, isoprenaline and phenylephrine and was decreased by vasoactive intestinal peptide (VIP), neurotensin and carbachol. Substances whose actions are modulated by prostaglandins and enhanced by prostaglandin synthesis inhibitors and which elevate blood monocyte and nervous tissue levels of cyclic GMP tended to increase lymphocyte traffic through peripheral lymph nodes in sheep in vivo. The opposite effect tended to be produced by substances whose actions require or are associated with prostaglandins or histamine, and which affect blood monocytic cyclic nucleotide levels by elevation of cyclic AMP or depression of cyclic GMP. Pain and inflammation tended to increase lymphocyte traffic, while analgesics and immunomodulators tended to decrease it.
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PMID:Modification of lymphocyte traffic by vasoactive neurotransmitter substances. 614 65

Vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) were studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to ICD-9 and the group of depressions was further classified according to the Newcastle Rating Scales for depression (Carney et al. 1965) (N-I). In the group of non-endogenously depressed patients, CSF-VIP levels (median 16 pmol/l) were found to be significantly lower than those of controls (median = 32 pmol/l) and endogenous depressives (36 pmol/l). In the non-endogenous group, it appeared that the low CSF-VIP was due to a group of patients who, during a past or present depressive episode, had been diagnosed as suffering from endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worse in the evening), and 'lack of clearly circumscribed episodes'. In many aspects this group seems similar to the atypical depressives described as monoamine oxidase inhibitor responders. Concerning CSF-CCK and CSF-gastrin, no significant differences between the examined groups were demonstrated.
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PMID:Vasoactive intestinal polypeptide decreased in cerebrospinal fluid (CSF) in atypical depression. Vasoactive intestinal polypeptide, cholecystokinin and gastrin in CSF in psychiatric disorders. 624 Dec 14

Young rats were fed on an essential fatty acid (EFA)-deprived diet for 6 weeks after weaning. Their pituitary was removed and adenohypophyseal cells dispersed and maintained in culture. Membrane lipids were analyzed and basal and stimulated levels of hormone secretion were measured after 4-day incubation in a culture medium containing or not 160 microM arachidonic acid 20:4n-6 (AA) in order to obtain EFA-deficient or EFA-restored pituitary cells, respectively. In EFA-deficient cells membrane phosphoglycerides (PGL) were depleted in AA and adrenic acid 22:4n-6; the deficit was overcome by incubation in the presence of AA. Depletion diversely affected PGL classes. AA was highly depleted in choline phosphoglycerides (ChoPG), only moderately depleted in serine and ethanolamine phosphoglycerides (SerPG and EtnPG) and not depleted at all in inositol phosphoglycerides, suggesting preferential preservation of AA in that class of PGL. Restoration of AA by addition of the fatty acid to the culture medium was complete for ChoPG and EtnPG and only partial for SerPG. Depressed levels of AA and adrenic acid in PGL were compensated for by a concomitant increase in 20:3n-9 and 22:3n-9. Growth hormone and prolactin (PRL) secretion was assessed by radioimmunoassay and possible effects of a membrane AA deficit on hormone regulation were tested in cells challenged by either growth hormone-releasing hormone, thyrotropin-releasing hormone, angiotensin II (AII), vasoactive intestinal peptide (VIP) or dopamine. Neither basal nor stimulated growth hormone secretion was different from controls in EFA-deficient cells. PRL modulation by VIP or dopamine was not affected either in EFA-deficient cells. In contrast, the capacity of AII, but not of thyrotropin-releasing hormone, to release PRL was markedly decreased in EFA-deprived cells. It was restored by addition of AA to the incubation medium. Parallel depression of AII-induced inositol phosphates and cAMP accumulation was also observed after EFA deficiency. When tested on membranes, the paradoxical inhibition of adenylate cyclase by AII documented by previous observations was reinforced in EFA-deficient membranes. In contrast, binding of AII was not affected by EFA deficiency. It is concluded that under our experimental conditions EFA deficiency affects selectively coupling of the AII receptor to its effectors without alteration of binding. The effect could involve changes in receptor interactions with coupling proteins.
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PMID:Selective effect of a diet-induced decrease in the arachidonic acid membrane-phospholipid content on in vitro phospholipase C and adenylate cyclase-mediated pituitary response to angiotensin II. 782 82

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel vasoactive intestinal peptide (VIP)-like peptide isolated from ovine hypothalami. The presence of PACAP-like immunoreactivity was recently demonstrated in nerve cell bodies of sensory ganglia in the rat. Since PACAP belongs to a large family of chemically related neuropeptides, we have, in the present study, tried to establish the synthesis of PACAP in neurons of sensory ganglia, using in situ hybridization with a 35S-labelled oligonucleotide probe complementary to PACAP mRNA. The expression of PACAP was compared to that of calcitonin gene-related peptide (CGRP) using a radiolabelled CGRP oligonucleotide probe. The PACAP probe labelled small to medium-sized neurons in the trigeminal ganglion and dorsal root ganglia at different levels, indicating the presence of PACAP mRNA. The CGRP probe labelled nerve cell bodies of varying size, outnumbering those labelled by the PACAP probe. In dorsal root ganglia, cells expressing PACAP constituted c. 10% and those expressing CGRP 46% of the total number of nerve cell bodies. Expression of PACAP was seen in a small subpopulation of cells expressing CGRP. We conclude that PACAP is synthesized in a subpopulation of neurons of sensory ganglia in the rat. Therefore, the recently described effects of PACAP--cutaneous vasodilation, potentiation of oedema formation and depression of nociceptive spinal reflexes--may be physiological and related to neurogenic inflammation and modulation of pain transmission.
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PMID:Pituitary adenylate cyclase activating polypeptide expression in sensory neurons. 789 55

The release of motilin from an isolated preparation of pig duodenum has been studied. There different types of stimuli were applied: electrical nerve stimulation, intraarterially administered peptides, and instillation of test solutions into the lumen of the duodenum. Furthermore extracts of 20 different regions of the pig digestive system have been analyzed for motilin content. Analysis of the extracts only detected significant presence of motilin in the pig duodenum and jejunum (79 +/- 15 and 60 +/- 19 pmol/g). The stimulation experiments showed: (1) a significant noncholinergic depression of motilin release during electrical stimulation of the vagus nerve (nadir at 74 +/- 5% of baseline level; (2) a significant elevation of motilin release in response to intraarterially administered vasoactive intestinal peptide (VIP) (peak at 330 +/- 35% of baseline level), and (3) a significantly elevated motilin release in response to instillation of autologuous bile (peak at 170 +/- 16% of baseline level) and hydrochloric acid (peak at 196 +/- 42% of baseline level) into the duodenal lumen. In conclusion, luminal acidification and bile are important factors in stimulation of motilin release, whereas the vagally stimulated VIP release was insufficient to overcome the general inhibitory effect of vagus stimulation.
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PMID:Regulation of motilin release from isolated perfused pig duodenum. 888 78

Results from preclinical studies have validated the participation of neuropeptides in sleep regulation. In recent human and clinical studies it has been shown that peripheral administration of various peptides results in specific changes in the sleep electroencephalogram in humans. Furthermore, it has been demonstrated that certain peptides are common regulators of the electrophysiological and neuroendocrine components of sleep. It is now well established that the balance between the neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in normal and pathological sleep regulation. In young normal subjects, GHRH stimulates slow-wave sleep and growth hormone secretion but inhibits cortisol release, whereas CRH has the opposite effect. During normal aging and during acute depression, the GHRH:CRH ratio is changed in favor of CRH, resulting in disturbances in sleep endocrine activity. In addition to GHRH, galanin, growth hormone-releasing peptide, and neuropeptide Y also promote sleep, unlike ACTH(4-9), which disturbs sleep. In elderly subjects, sleep deteriorates after acute administration of somatostatin but improves after chronic treatment with vasopressin. Vasoactive intestinal polypeptide decelerates the non-rapid eye movement-rapid eye movement cycle and advances the occurrence of the cortisol nadir. The impact of delta sleep-inducing peptide, cholecystokinin, and thyrotropin-releasing hormone on human sleep regulation is not yet clear. This paper reviews recent work investigating the influence of these various neuropeptides on sleep.
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PMID:Neuropeptides and human sleep. 945 70

In the rat neocortex, a subset of GABAergic interneurons express the neuropeptide vasoactive intestinal peptide (VIP). Previously, we demonstrated that a population of VIPergic interneurons could be accurately identified by their irregular spiking (IS) pattern and their bipolar morphology. IS interneurons were studied in neocortical slices from 16-22-day-old rats using whole-cell recordings, intracellular labelling and single-cell RT-PCR. In response to a depolarizing pulse, IS interneurons typically discharged a burst of action potentials followed by spikes emitted at an irregular frequency. Several seconds of depolarization, micromolar concentrations of 4-aminopyridine, and nanomolar concentrations of either dendrotoxin I or K converted this irregular pattern to a sustained discharge, suggesting the involvement of an ID-like K+ current. The main glutamate receptor subunits detected in IS cells were GluR1 flop and GluR2 flop, GluR5 and GluR6, and NR2B and NR2D for the alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartic acid (NMDA) subtypes, respectively. Paired whole-cell patch-clamp recordings indicated that pyramidal neurons provide intracortical glutamatergic inputs onto IS interneurons. Most connections had high probabilities of response and exhibited frequency-dependent paired pulse depression. Comparison of the amplitude distribution of paired responses suggested that most of these connections consisted of multiple functional release sites. Finally, two discrete subpopulations of IS cells could be identified based on the duration of the initial burst of action potentials and the differential expression of calretinin and choline acetyltransferase.
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PMID:Properties of bipolar VIPergic interneurons and their excitation by pyramidal neurons in the rat neocortex. 987 41


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