Effect of β-endorphin on pulsatile luteinizing hormone release in conscious castrated rats

The effect of intraventricular administration of β-endorphin on pulsatile LH release in castrated conscious rats was studied. The administration of 1 μg of β-endorphin into the lateral ventricle inhibited pulsatile discharge of LH secretion. Intravenous administration of naloxone blocked the suppressive effect of β-endorphin on LH release. These results suggest a possible role of β-endorphin, in addition to Met⁵-enkephalin, in the control of LH release in male rats.     

Cell apoptosis in the testis of male rats is elevated by intervention with β-endorphin and the mu opioid receptor

β-endorphin (β-EP) is involved in the regulation of male germ cells; however, little is known about the effect of β-EP on primary germ cells via opioid receptors. In this study, we first revealed significant cell apoptosis in the testis of male rats after β-EP intervention. Subsequently, the expression of the mu opioid receptor (MOR) was detected in both Leydig cells (LCs) and spermatogonia (SGs) by fluorescence colocalization; overlapping signals were also detected in apoptotic cells. In addition, LCs and SGs were separated from the testis of male rats and primary cells were treated with β-EP; this increased the mRNA levels of MOR and was accompanied by acute cell apoptosis. Our findings provide a foundation for the further study of apoptosis in reproductive cells regulated by β-EP and the MOR receptor.     

Human β-endorphin: Development of tolerance and behavioral activity in rats

Human β-endorphin produced a potent antinociceptive response as estimated by the tail-flick test in rats after intraventricular injection. On a molar basis, the peptide was 21 times more potent than morphine and in addition, the peptide produced morphine-like catatonia and hypothermia. These responses were blocked by naloxone. Repeated injections of the peptide induced tolerance to analgesic response, catatonia and hypothermia. Cross tolerance to morphine was also observed.     

The effect of β-endorphin on arginine-induced growth hormone and prolactin release

β-endorphin administration via constant infusion inhibited the release of growth hormone (GH) and augmented the release of prolactin (PRL) induced by arginine in normal female subjects. Although β-endorphin infusion also induced hyperglycemia, the increment in plasma glucose was insufficient to account for the observed suppression of arginine-initiated GH release. These studies demonstrate that β-endorphin influences, in opposed directions, the secretion of PRL and GH in women.     

Comparison of the behavioral effects of β-endorphin and enkephalin analogs

The behavioral effects of β-endorphin, enkephalin analogs, morphine and etorphine were briefly compared. In the tail-flick test in mice and in the wet shake test in rats, β-endorphin and D-Ala²-D-Leu⁵-enkephalin had equal antinociceptive activity; D-Ala² -Met-enkephalinamide and D-Leu⁵-enkephalin were less active. The order of activity of the enkephalin analogs and opiate alkaloids for stimulating locomotor activity in mice paralleled their analgesic activities; β-endorphin, however, had only minimal stimulatory actions. Morphine sulfate, 50 μg injected into the periaqueductal gray, produced hyperactivity but this effect was not observed with etorphine or opioid peptides. By contrast, “wet dog” shakes was observed with the opioid peptides but not with either opiate alkaloid. These heterogenous behavioral responses, which were all antagonized by naloxone, indicate that multiple types of receptors mediate the effects of opiates in the central nervous system.     

Differential control of β-endorphin/β-lipotropin secretion from anterior and intermediate lobes of the rat pituitary gland in vitro

The secretion of immunoreactive β-endorphin (β-END_i) and β-lipotropin (β-LPH_i) by neurointermediate lobes (NIL) and anterior lobe (AL) cells of the rat pituitary gland was studied in an $\text{in vitro}$ superfusion system. Peptides were characterized by gel chromatography on Sephadex G-50 and by two radioimmunoassays: a β-LPH assay in which β-END did not crossreact (β-LPH_i) and a β-END/β-LPH assay in which β-END and β-LPH showed full crossreactivity (β-END_i/β-LPH_i).$\text{Intermediate lobe}$. The spontaneous secretion of β-END_i/β-LPH_i by the NIL was 1–2 ng/min/lobe. Chromatography showed that 97% of this β-END_i/β-LPH_i eluted at the position of β-END. Dopamine inhibited the spontaneous secretion of β-END and the dopamine-receptor blocker domperidone prevented this inhibition. Isoprenaline caused a 3–4 fold stimulation of the secretion of β-END. The β-adrenergic receptor blocker propranolol abolished this stimulation. Hypothalamic extract, lys-vasopressin, 5-hydroxytryptamine and histamine were ineffective in changing the spontaneous secretion of β-END_i/β-LPH_i.$\text{Anterior lobe}$. The spontaneous secretion of β-END_i/β-LPH_i by AL cells was 0.15–0.20 ng/min/10⁵ cells. Chromatography revealed that about 70% of this material behaved like β-LPH, 30% behaved like β-END. Hypothalamic extract and lys-vasopressin induced a 3–5 fold increase in the secretion of both β-END and β-LPH. Catecholamine, 5-hydroxytryptamine and histamine were ineffective in changing the spontaneous secretion of β-END_i/β-LPH_i.These results indicate that β-END is the predominant β-LPH-related peptide secreted by the intermediate lobe and that its secretion is inhibited via a dopaminergic receptor mechanism and stimulated via a β-adrenergic receptor mechanism. The secretion of β-END and β-LPH by the anterior lobe is not affected by catecholamines but is stimulated by CRF and vasopressin.     

Ultrastructural localization of corticotropin, β-lipotropin,and αand β-endorphin in the porcine anterior pituitary

Summary The peroxidase-antiperoxidase immunocytochemical technique was used to identify the ACTH/endorphin cells in the porcine pituitary at the ultrastructural level and to determine the precise subcellular localization of the pro-ACTH/endorphin fragments. The cells display different aspects: 1) large, regular shapes with numerous and large secretory granules; 2) small, irregular and angular shapes with small granules aligned along the periphery of the cell; and 3) intermediate forms. The presence of and -endorphin not only in the same cells but also in the same secretory granules that contain ACTH and -LPH clearly indicates that both the precursor or its fragments and the abovementioned peptides are stored in the same granules and released simultaneously by the corticotropic cells. The presence of FSH in some corticotropic cells is also discussed.Abbreviations used in this Article ACTH corticotropin - -MSH -melanotropin (ACTH I–I3) - CLIP corticotropin-like intermediate lobe peptide (ACTH 18–39) - -LPH -lipotropin - -MSH -melanotropin (-LPH 41–58); -endorphin (-LPH 61–91); -endorphin (-LPH 61–76)     

Quantitative mapping of cocaine-induced ΔFosB expression in the striatum of male and female rats

ΔFosB plays a critical role in drug-induced long-term changes in the brain. In the current study, we evaluated locomotor activity in male and female rats treated with saline or cocaine for 2 weeks and quantitatively mapped ΔFosB expression in the dorsal striatum and nucleus accumbens of each animal by using an anti-FosB antibody that recognizes ΔFosB isoforms preferentially. Behavioral analysis showed that while there was little difference between males and females that sensitized to cocaine, nonsensitizing rats showed a large sex difference. Nonsensitizing males showed low behavioral activation in response to cocaine on the first day of treatment, and their activity remained low. In contrast, nonsensitizing females showed high activation on the first day of treatment and their activity remained high. Western blot and immunohistochemical analyses indicated that basal levels of ΔFosB were higher in the nucleus accumbens than the dorsal striatum, but that the effect of cocaine on ΔFosB was greater in the dorsal striatum. Immunostaining showed that the effect of cocaine in both the dorsal striatum and nucleus accumbens was primarily to increase the intensity of ΔFosB immunoreactivity in individual neurons, rather than to increase the number of cells that express ΔFosB. Detailed mapping of ΔFosB-labeled nuclei showed that basal ΔFosB levels were highest in the medial portion of the dorsal striatum and dorsomedial accumbens, particularly adjacent to the lateral ventricle, whereas the cocaine-induced increase in ΔFosB was most pronounced in the lateral dorsal striatum, where basal ΔFosB expression was lowest. Sex differences in ΔFosB expression were small and independent of cocaine treatment. We discuss implications of the sex difference in locomotor activation and regionally-specific ΔFosB induction by cocaine.     

The effect of environment on plasma cortisol and β-endorphin in the parturient pig and the involvement of endogenous opioids

Previous work has indicated that plasma cortisol increases during farrowing in the pig suggesting increasing physiological stress. The aim of this study was to determine changes in plasma cortisol and β-endorphin over farrowing in the pig to obtain a more detailed profile of pituitary and adrenal release at this time and also to investigate the involvement of endogenous opioids in the mediation of the HPA axis. Indwelling jugular catheters were implanted, under general anaesthesia, in 31 Large White×Landrace gilts approximately 15 days before the expected parturition day (EPD). Gilts were moved into either a farrowing crate, without straw (n=15), or a straw-bedded pen (n=16) 5 days before the EPD. Samples were taken during the pre-farrowing period and then during farrowing itself. At 7.5 min after the birth of the first piglet (BFP), gilts either received naloxone, an opioid antagonist, (1 mg kg⁻¹ body weight, i.v.) or a control dose of saline. Plasma β-endorphin increased following the BFP but remained fairly constant over the third and fourth hour of farrowing. Plasma cortisol continued to increase over the 4 h following the BFP. Changes seen in these hormones were generally insensitive to the environment and there was little evidence of opioid mediation of the HPA axis at parturition. From these results it is suggested that certain aspect(s) of parturition itself stimulate the HPA axis. However it is unknown if the rise in plasma cortisol is a result of some stress-inducing factor of the parturition process or whether it reflects a metabolic function. The study also demonstrates the lack of any inhibitory mediation of the HPA axis by endogenous opioids at parturition.     

Structure and catalytic mechanism of the β-carbonic anhydrases

The β-carbonic anhydrases (β-CAs) are a diverse but structurally related group of zinc-metalloenzymes found in eubacteria, plant chloroplasts, red and green algae, and in the Archaea. The enzyme catalyzes the rapid interconversion of CO₂ and H₂O to HCO₃⁻ and H⁺, and is believed to be associated with metabolic enzymes that consume or produce CO₂ or HCO₃⁻. For many organisms, β-CA is essential for growth at atmospheric concentrations of CO₂. Of the five evolutionarily distinct classes of carbonic anhydrase, β-CA is the only one known to exhibit allosterism. Here we review the structure and catalytic mechanism of β-CA, including the structural basis for allosteric regulation.     

Nonopioid effect of β-endorphin

This review presents the generalized literature data and the results of our own research of the nonopioid effect of β-endorphin, an opioid neuropeptide interacting not only with opioid but also with nonopioid (insensitive to the opioid antagonist naloxone) receptors. The roles of the hormone and its receptors in regulation of the immune, nervous, and endocrine systems are discussed. The effect of neuromediator on the immune system mediated by both opioid and nonopioid receptors is considered in detail. The data on distribution and function of the nonopioid β-endorphin receptor in human and animal organisms are presented. All available data on the characteristics of the nonopioid β-endorphin receptor obtained by means of radioligand analysis are given. The discussed information is supposed to extend our conceptions of the role of β-endorphin in mammals and to be of extensive use in medicine and pharmacology.     

Immunoreactivity for β-endorphin in LH-RH neurons of the fetal human hypothalamus

Summary A peptide immunochemically related to -endorphin was detected in some LH-RH neurons of the fetal human hypothalamus by comparison of adjacent sections stained for -endorphin and for LH-RH. In the same section, by successive staining and after antibody elution, both peptides were again revealed in the same neuron. The significance of the presence of the -endorphin-like material in LH-RH neurons is discussed.     

Cross tolerance between morphine and β-endorphin in vivo

Experiments were performed to establish the development of cross tolerance between morphine and the C-terminal fragment of porcine β-lipotropin /LPH_61–91, β-endorphin/ in rats. Repeated intracerebroventricular /ICV/ or peripheral administration of morphine induced tolerance both to morphine and β-endorphin. The tolerance induced by ICV administration of morphine was more pronounced than in the case of peripheral application. The results give support to the theory that at least in part similar sites and mechanisms are involved in the analgesic activity of morphine and the endorphins.     

Distribution of acid phosphatase and β-glucuronidase in the hypoplastic cerebellum of jaundiced Gunn rats

Summary Activities of acid phosphatase and -glucuronidase in the cerebella of young jaundiced (j/j) and non-jaundiced (j/+; control) Gunn rats were studied with the enzyme histochemical method. The cerebellum of j/+ rats showed high acid phosphatase activities in Purkinje cells and neurons in the cerebellar nuclei. In j/j rats, a number of neurons were lost and numerous microglialike cells with a high acid phosphatase activity appeared in the hypoplastic cerebellum. Although -glucuronidase activity was rarely detected in the control cerebellum, a high enzyme activity was observed associated with microglialike cells in j/j rats. The present results provide a cytological basis for the reported differential increase in the activities of these lysosomal enzymes in the j/j rat cerebellum.     

Neuronal cholecystokinin,gastrin-releasing peptide,neurotensin, and β-endorphin in the intestine of the guinea pig

Summary The guinea-pig intestine was found to harbor nerve fibers containing immunoreactive cholecystokinin (CCK), gastrin-releasing peptide (GRP), neurotensin or - endorphin. Such fibers occurred in the myenteric and submucous ganglia and in the smooth muscle. GRP- and CCK-fibers, in addition, were found in the mucosa. Following colchicine treatment, neuronal perikarya in the myenteric ganglia displayed CCK-, GRP-, or -endorphin immunoreactivity. CCK-immunoreactive perikarya were located also in the submucous ganglia. Neurotensin-immunoreactive cell bodies could not be detected. The presence of immunoreactive neuronal perikarya in intramural ganglia indicates that CCK-, GRP- and -endorphin-containing fibers are intrinsic to the gut wall. GRP, neurotensin, and -endorphin were identified in extracts of smooth muscle by immunochemical and Chromatographic analysis.CCK-8, GRP and neurotensin contracted the isolated taenia coli. Tetrodotoxin reduced the response to CCK-8 but not that to GRP and neurotensin, suggesting that the two latter peptides act directly on smooth muscle receptors. The effect of CCK-8 is partly mediated by cholinergic nerves, since not only tetrodotoxin but also atropine greatly reduced the CCK-8-induced contractile response. The substance P (SP) antagonist, (d-Pro², d-Trp^7,9)-SP_1–11 had no effect on the CCK-8-induced contraction of the taenia. CCK-8 enhanced the SP-mediated (atropine-resistant) contractile response to electrical stimulation but not that mediated by acetylcholine. -Endorphin had no effect on the tension of the muscle but reduced the response to electrical stimulation (cholinergic as well as SP-mediated) through a naloxone-sensitive mechanism.While CCK-8 and -endorphin seem to play neuromodulatory roles in the taenia coli, the significance of GRP and neurotensin remains enigmatic.     

Immunohistochemical localization of transforming growth factor α in the major salivary glands of male and female rats

Summary The three major salivary glands of normal male and female Fischer 344 rats of different ages were examined for the localization of epidermal growth factor (EGF) and transforming growth factor (TGF) by immunohistochemical staining. EGF was demonstrated only in the granulated convoluted tubule (GCT) cells of the submandibular gland, the results confirming the previous reports, and most abundantly in adult males and pregnant females. TGF stain was localized in all three glands and was found throughout the entire duct system, excluding acinar cells. The myoepithelial cells of the sublingual gland were also reactive with the TGF antibody. The specificity of the staining was confirmed by negative staining reaction with the absorbed antibody and by radio-immunoassay and Western blot methods. This is the first report describing the presence of TGF in the rat salivary glands.     

Specificities of β1 integrin signaling in the control of cell adhesion and adhesive strength

Cells exert actomyosin contractility and cytoskeleton-dependent force in response to matrix stiffness cues. Cells dynamically adapt to force by modifying their behavior and remodeling their microenvironment. This adaptation is favored by integrin activation switch and their ability to modulate their clustering and the assembly of an intracellular hub in response to force. Indeed integrins are mechanoreceptors and mediate mechanotransduction by transferring forces to specific adhesion proteins into focal adhesions which are sensitive to tension and activate intracellular signals. α(5)β(1) integrin is considered of major importance for the formation of an elaborate meshwork of fibronectin fibrils and for the extracellular matrix deposition and remodeling. Here we summarize recent progress in the study of mechanisms regulating the activation cycle of β(1) integrin and the specificity of α(5)β(1) integrin in mechanotransduction.