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)

VIP dose-dependently increased basal, but not submaximally ACTH (10(-10) M)-stimulated, aldosterone (ALDO) and corticosterone (B) secretion of dispersed rat capsular and inner adrenocortical cells, respectively. The maximal stimulatory effect (60-70% rise) was obtained with a VIP concentration of 10(-8) M. [4-Cl-D-Phe6,Leu17]-VIP, a VIP-receptor antagonist (VIP-A), and corticotropin-inhibiting peptide (CIP), an ACTH receptor antagonist (both 10(-6) M), completely annulled VIP (10(-8) M)-evoked rises in basal ALDO and corticosterone secretions. The ACTH (10(-10) M)-enhanced (about 5-fold) production of both hormones was completely reversed by CIP (10(-6) M) and only partially reduced (about -30%) by VIP-A (10(-6) M). The hypothesis is advanced that the weak secretagogue effect of VIP on dispersed rat capsular and inner adrenocortical cells may be due to its positive interaction with ACTH receptors.
 ...
PMID:Stimulatory effect of vasoactive intestinal peptide (VIP) on the secretory activity of dispersed rat adrenocortical cells. Evidence for the interaction of VIP with ACTH receptors. 818 Jan 11

Several peptides exhibiting hypnogenic properties when administered i.p., i.v. or i.c.v. are now known. No data, however, are available concerning their targets in the brain. In the present work we hypothesize that the nucleus raphe dorsalis (nRD) may be one such target since it contains 2 sleep permissive components that must be influenced for sleep to occur. One of these components is serotoninergic in nature and gates the occurrence of ponto-geniculo-occipital (PGO) waves. The other, of unknown nature, influences tonic sleep phenomena. For hypnogenic peptides, a putative mechanism permitting the triggering and maintenance of sleep might consist of influencing both the above components. In the present work, 3 hypnogenic substances, CLIP (corticotropin-Like intermediate lobe peptide), VIP (vasoactive intestinal polypeptide) and DSIP (delta sleep inducing peptide), were injected into the nRD in order to determine whether these compounds still induce sleep by local administration. To verify that such local injections do not spread outside the nRD, radiolabelled CLIP and VIP were also injected. Autoradiograms obtained with either labeled CLIP or VIP indicate that these compounds, injected in a 0.2 microliter volume, do not spread outside the nRD. The sleep data obtained confirm that CLIP, at a dose of 10 ng, induces an increase in duration of paradoxical sleep (PS); this effect is observed only for injection sites located in the dorsolateral part of the nRD, an area where CLIP immunoreactive (IR) fibers are present. VIP, at a dose of 100 ng, also increases PS duration, whereas at 10 ng, only slow wave sleep duration is increased. In this case, the positive injection sites are scattered throughout the entire nRD as are the VIP-IR fibers. With DSIP, no sleep effect was found whatever the dose used or the site injected; in the same manner, no DSIP-IR fibers have been located in this structure. These data suggest that the nRD is a target for the expression of the hypnogenic properties of CLIP and VIP, but not for DSIP. The nature of the possible mechanisms permitting such expression are discussed.
 ...
PMID:Is the nucleus raphe dorsalis a target for the peptides possessing hypnogenic properties? 818 Jul 98

Among vertebrates, there is an extreme conservation in amino acid sequence for the neuropeptide PACAP-38 and its C-terminal shortened derivative PACAP-27. The PACAP gene is assigned to chromosome 18 in man and its organization has been characterized. PACAP-38 and its minor derivative PACAP-27 are widely distributed in the central nervous system. PACAP-38 is particularly abundant in hypothalamus. The mapping of the afferentation and efferentation of PACAP systems are progressively delineated, including a search for the colocalization with other neurotransmitters. In several peripheral organs positive neuronal perikarya and fibers are also seen. PACAP acts through two types of receptors: (1) the highly selective type I that displays a 500 to 2000 selectivity for PACAP-38 and PACAP-27 as compared to VIP; (2) type II is the so-called VIP receptor showing similar high affinity for PACAP-38, PACAP-27 and VIP. It is less selective, therefore, than previously thought. This is why this second receptor, qualifying as an unspecific VIP-PACAP receptor, is hardly considered here. Type I receptors can stimulate two enzymes: the adenylate cyclase and phospholipase C (whose activation leads to the inositol phosphate-cytosolic Ca2+ cascade). This dual coupling may have several distal consequences including on gene expression, cell growth and differentiation. Although a relatively comprehensive spectrum of pharmacological activities has already been established we still need to limit the physiological roles of PACAP as neurotransmitter and/or neuromodulator. Concerning the hypothalamo-pituitary axis, PACAP reduces food intake in mice and raises plasma arginine vasopressin in rat, probably through PACAP-ir neurons in paraventricular and supraoptic nuclei projecting to the neurohypophysis. PACAP originating in the hypothalamus may also be transported to the anterior pituitary through portal vessels. Data on the antehypophysis suggest a role on i.a. reproduction and growth. PACAP stimulates adenylate cyclase and increases [Ca2+] in gonadotropes, somatotropes, and folliculo-stellate cells. It elevates the secretion of alpha-MSH from melanotropes, and that of interleukin-6 from pituitary folliculo-stellate cells. PACAP potentiates the effects of LHRH on LH and FSH secretion. More clearly perhaps, PACAP increases the synthesis of LH, GH, PRL and ACTH after 1-2 days. In human pathology, PACAP-27 and PACAP-38 stimulate adenylate cyclase activity in membranes from 'null'-, gonadotropin-, GH-, and ACTH-producing pituitary adenomas but are inactive in prolactinomas.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Type I receptors for PACAP (a neuropeptide even more important than VIP?). 821 37

A neutral endopeptidase (NEP) from Lactococcus lactis has recently been cloned and shown to contain high sequence homology with the human neutral endopeptidase, endopeptidase 24.11 (I. Mierau et al., J. Bacteriol. 175, 2087-2096, 1993). The gene for the neutral endopeptidase from L. lactis was cloned into the pQE expression vector, resulting in the fusion of a hexahistidine at the N-terminus. The recombinant enzyme was expressed to high levels in Escherichia coli (approximately 10 mg/liter of culture) and purified to homogeneity in a two-step procedure. A number of peptides were studied as substrates for the enzyme. The enzyme cleaves the following peptides at the Gly3-Phe4 bond: enkephalins, dynorphins A-6, A-8, A-9, A-10, A-13, and A-17, and alpha-neo-endorphin. In addition the enzyme hydrolyzes bradykinin, substance P, beta-endorphin, ACTH, and VIP. Although the cleavage patterns observed are similar to that seen with mammalian neutral endopeptidase, the lactococcal enzyme more efficiently cleaves larger peptide substrates. As observed with the mammalian neutral endopeptidase, the lactococcal enzyme exhibits higher kcat/K(m) values for the enkephalins than for their corresponding amides, indicating the functionality of an active-site arginine. Inactivation of the lactococcal endopeptidase by diethyl pyrocarbonate and protection afforded by the substrate dynorphin A-6 indicate the functionality of a positionally conserved active-site histidine. This was confirmed by demonstrating that conversion of this histidine, histidine 587, to glutamine generated inactive enzyme. Similarly, conversion of the putative zinc ligand glutamate 535 to glutamine led to inactive enzyme. These studies indicate a conservation of critical catalytic residues between the two enzymes and suggest that the lactococcal endopeptidase is a better model than thermolysin for the mammalian enzyme.
 ...
PMID:Heterologous expression and characterization of recombinant Lactococcus lactis neutral endopeptidase (neprilysin). 880 62

The effect of VIP on mast cell invasion/degranulation in testicular interstitium of stressed (immobilization and cold) and beta-endorphin-treated rats were investigated. Fifty-three Wistar male rats were used in four series of experiments. Initially, the effect of immobilization and cold stress on mast cell invasion and degranulation in testicular interstitium was examined in three age group of rats: 15 (n = 6), 30 (n = 6), and 45 (n = 7) days of age. Five animals per age group were used as controls. Because the most obvious effect of the stress on mast cell invasion/degranulation in testicular interstitium was observed in 45-day-old rats, the action of VIP in stressed and beta-endorphin-treated rats was only investigated at this age group. Mast cells and Leydig cells were evaluated by using histochemical and light microscopic protocols. Stress caused mast cell accumulation and degranulation in the testicular interstitium. Stress decreased heparin synthesis and possibly increased histamine content of mast cells. The effect of beta-endorphin was not as high as seen with stress. In some areas of testicular interstitium of stressed rats, there were aplasic and/or inactive Leydig cells. VIP inhibited proliferation and degranulation of mast cells, increased heparin content of the cells, and protected Leydig cells. By way of mast cell accumulation and degranulation in the testicular interstitium, exposure to stress may lead to Leydig cell damage and infertility. VIP may be involved in the protection of normal testicular function under stress conditions.
 ...
PMID:The effect of vasoactive intestinal peptide (VIP) on mast cell invasion/degranulation in testicular interstitium of immobilized + cold stressed and beta-endorphin-treated rats. 884 72

Multiple communicative pathways among the nervous, endocrine and immune systems facilitate physiological immunoregulation. Spinal cord injury (SCI) patients have decreased natural (NK cell) and adaptive (T cell) immune function and reduced blood levels of cellular adhesion molecules (CAMs) that participate in immune function and wound healing. We found decreased LFA-1 and VLA-4 on peripheral blood leukocytes in SCI patients and lower levels of CAMs in SCI patients with pressure ulcers than in those without them. SCI might affect immune cells and immune responsiveness by: (1) disrupting the outflow of signals from the sympathetic nervous system to lymphoid tissues and their blood vessels as well as the returning afferent signals from these tissues to the brain; (2) immunosuppression caused by the stressors affecting SCI patients; (3) interrupting returning signals to the CNS from the periphery thereby reducing facilitation of immunoregulatory CNS neurons and decreasing their activity; or a combination of all three. SCI patients may develop dysregulation of the sympathetic nervous system that is intimately involved in immune function. Chronic stress mediates immunosuppression by corticosteroids, catecholamines, endorphins and met-enkephalin. The hypothalamus coordinates the response to stress through the release of soluble products from the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Whereas the nervous and endocrine systems are not concerned with immunological specificity, they do influence the intensity, kinetics and localization of immune responses. Products of an activated immune system may generate feedback circuits capable of inhibiting, enhancing or regulating neuronal input. Immune system cells can produce neurologically active peptides including ACTH, CRF, growth hormone, thyrotropin, prolactin, human chorionic gonadotropin, endorphin, enkephalins, substance P, somatostatin and VIP. Cytokines are likely important mediators of the HPA response to immune stimuli.
 ...
PMID:Immune system-neuroendocrine dysregulation in spinal cord injury. 898 97

The presence of putative neuromodulators in the nerve fibres was investigated in white skeletal muscle of two teleost fish not taxonomically correlated and showing different patterns of innervation (multiple versus focal innervation). Cryostat sections of epaxial, hypaxial and adductor mandibulae (AM) muscles of Sparus aurata and Anguilla anguilla were stained histochemically for reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase. Other sections were used for indirect immunohistochemistry (streptavidin-biotin and rhodamine immunofluorescence methods), employing antibodies specific for putative excitatory or inhibitory peptides, including CGRP, substance P, met-enkephalin, bombesin, and VIP. In addition, ultrastructural observations were performed in order to describe the morphology of the motor endplates. A strong immunoreactivity for CGRP and substance P was found in many nerve terminals. Met-enkephalin, bombesin and VIP immunoreactivities were less frequently observed. No immunoreactivity was observed to CCK, NPY or 5-HT. NADPH-diaphorase was identified in nerve fibres of the AM complex only of A. anguilla. Electron microscopy observations evidenced more than one type of synaptic vesicle in motor endplates. Some differences in putative neuromodulator distributions were observed in the two species and muscle complexes, which may be related to the different taxonomical position as well as the different pattern of innervation of white muscle fibres.
 ...
PMID:Different putative neuromodulators are present in the nerves which distribute to the teleost skeletal muscle. 981 Apr 86

Specimens of testis, excurrent duct including the accessory genital glands and urethra throughout its extension were investigated in adult bovines, in order to immunohistochemically localize both the peptidergic innervation and the epithelial cell types belonging to the diffuse endocrine system (DES). Immunoreactivities to GRP, met- and leu-enkephalins, CGRP, NPY, substance P, VIP, somatostatin, beta-endorphin and 5-HT antisera were tested by means of a labelled streptavidin-biotin (LSAB) method. Such regulatory substances were found in components of the peripheral nervous system (nerve fibers in the connective and muscular tissues, sub- and intrapithelial nerve terminals, nerve cells bodies and fibers in intramural ganglia), and in epithelial endocrine/paracrine cells. Bovine urogenital apparatus is supplied by many peptide-containing nerves, which contain in many localizations GRP and enkephalins, and to a lesser extent substance P, CGRP, NPY and VIP. A thin network of peptidergic nerves distributes to the musculature of the canalicular organs and accessory glands. The prostatic complex was especially rich in peptidergic innervation, and also contained somatostatin- and 5-HT-secreting endocrine cells. In addition, 5-HT-immunoreactive endocrine cells were found in the bulbourethral gland and urethral epithelium. CGRP-ir nerves were present contacting striated muscle fibers of urethra (motor end plates). The testis was devoid of any immunoreactivity. These data are compared with those obtained in a companion study carried out the same organs in two species of Equidae (Equus caballus and Equus asinus). Different patterns of immunoreactivities can be outlined in these domestic ungulates.
 ...
PMID:Immunolocalization of regulatory peptides and 5-HT in bovine male urogenital apparatus. 981 May 1

Experimental research has recently shown that acupuncture induces the formation of opioid-like peptides (OLPs) in animals. In order to provide further evidence, we tested the beta-endorphin levels and other parameters (VIP, lymphocyte subsets, NK cells and monocyte phagocytosis) in a group of 90 patients suffering from various painful disorders treated with acupuncture. Zusanli (St 36) and Hegu (LI 4) acupoints were selected. A homogeneous group of 30 subjects was used as control. Evaluation of the above parameters was made with 3 series of blood tests before treatment, 30 minutes and 24 hours after acupuncture treatment. In the acupuncture group, the following results were achieved: 1) A considerable increase in beta-endorphin levels remained high even 24 hours after acupuncture treatment. In addition, we demonstrated an inverted correlation between beta-endorphins and VIP; 2) 30 minutes after acupuncture session, 80% of the treated patients showed a significant increase of CD3 and CD4 values and an increase of CD8 24 hours after stimulation; 3) Monocyte phagocytosis was increased in 45% of the treated subjects 30 minutes from starting treatment, and in 100% of them after 24 hours. The percentage of NK cells was also increased in 40% of cases after 30 minutes, and in 50% after 24 hours. However, in the control group, no such significant changes in immune parameters were found.
 ...
PMID:Effects of acupuncture on immune response related to opioid-like peptides. 1043 65

Gastric inhibitory polypeptide (GIP) is a 42-amino acid peptide, belonging to the VIP-secretin-glucagon superfamily, some members of this group are able to regulate adrenocortical function. GIP-receptor mRNA has been detected in the rat adrenal cortex, but investigations on the effect of GIP on steroid-hormone secretion in this species are lacking. Hence, we have investigated the distribution of GIP binding sites in the rat adrenal gland and the effect of their activation in vivo and in vitro. Autoradiography evidenced abundant [125I]GIP binding sites exclusively in the inner adrenocortical layers, and the computer-assisted densitometric analysis of autoradiograms demonstrated that binding was displaced by cold GIP, but not by either ACTH or the selective ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP). The intraperitoneal (IP) injection of GIP dose-dependently raised corticosterone, but not aldosterone plasma concentration: the maximal effective dose (10 nmol/rat) elicited a twofold increase. GIP did not affect aldosterone and cyclic-AMP release by dispersed zona glomerulosa cells. In contrast, GIP enhanced basal corticosterone secretion and cyclic-AMP release by dispersed inner adrenocortical cells in a concentration-dependent manner, and the maximal effective concentration (10(-7) M) evoked 1.5- and 2.4-fold rises in corticosterone and cyclic-AMP production, respectively. GIP (10(-7) M) did not display any additive or potentiating effect on corticosterone and cyclic-AMP responses to submaximal or maximal effective concentrations of ACTH. The corticosterone secretagogue action of 10(-7) M GIP was abolished by the protein kinase A (PKA) inhibitor H-89 (10(-5)M), and unaffected by CIP (10(-6)M). Collectively, these findings indicate that GIP exerts a moderate but statistically significant stimulatory effect on basal glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway.
 ...
PMID:Gastric inhibitory polypeptide stimulates glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase-dependent signaling pathway. 1046 10


<< Previous 1 2 3 4 5 6 Next >>