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)

A microperfusion system was developed to study detailed kinetics of adrenocorticotropic hormone (ACTH) secretion by dispersed rat anterior pituitary cells responding to various ACTH secretagogues. The system approaches hydrodynamics to square-wave stimuli and enables kinetic analysis of ACTH secretion with intervals as short as 5 sec. ACTH secretion initiated within 5 sec of exposure of the cells to corticotropin-releasing factor (CRF), arginine vasopressin (AVP), oxytocin (OT) or angiotensin II (A-II) and reached a maximum within 20-40 sec. CRF induced a plateau-shaped secretion of ACTH which remained constant as long as CRF was perifused. In contrast, the ACTH secretion responding to AVP, OT and A-II rose rapidly to a peak and fell to the baseline despite continued perifusion of these agents. There were two components of ACTH secretory response to AVP and OT. AVP had synergistic effect with CRF only if it was perifused simultaneously with CRF or immediately after CRF was stopped. The ACTH secretory response to A-II was greatly diminished when cells were exposed to AVP or OT before A-II perifusion. Prior exposure to A-II had no effect on the magnitude of the ACTH secretory response to either AVP or OT. Epinephrine, nor-epinephrine, gastrin-releasing peptide, atrial natriuretic factor and cholecystokinin stimulated no significant ACTH secretion in the microperfusion system, although some of them induced ACTH secretion by same cell preparation in static culture systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Physiological analyses of secretory kinetics of adrenocorticotropic hormone (ACTH) from anterior pituitary cells: development and application of a microperfusion system]. 131 80

Gastrin-releasing peptide (GRP; mammalian bombesin) may be involved in the neuroendocrine regulation of pituitary hormone secretion. We investigated the effect of GRP on ACTH secretion in conscious male rats. GRP (7-700 pmol) stimulated ACTH secretion dose-dependently after intracerebroventricular (icv) administration but had no effect after iv administration. GRP infused icv in a dose of 7 pmol, which alone increased ACTH 1.5-fold, potentiated the ACTH-releasing effect of arginine vasopressin (AVP; 80 pmol iv) and corticotropin-releasing hormone (CRH; 100 pmol iv). A higher dose of GRP (70 pmol icv), which stimulated ACTH secretion 2-fold, potentiated the effect of 80 and 400 pmol AVP iv, but had only additive effect on the ACTH response to 800 pmol AVP iv or 100 pmol CRH iv. GRP infused iv in a dose of 210 pmol, which in itself had no effect on ACTH secretion, potentiated the ACTH-stimulating effect of AVP and CRH approximately 2.5-fold. The effect of GRP (icv or iv) on AVP or CRH-stimulated ACTH release was only slightly smaller than the effect of combined administration of AVP and CRH (80 + 100 pmol iv). The ACTH-stimulating effect of GRP (700 pmol icv) was inhibited about 60% by pretreatment with either CRH or AVP antiserum and prevented by combined pretreatment with the antisera. The results indicate that: 1) GRP affects ACTH secretion indirectly at a suprapituitary level--possibly in the hypothalamus--by stimulating the release of AVP and CRH to the pituitary portal blood; and 2) GRP acts directly at the pituitary level to augment the effect of AVP and CRH on the corticotrophs. We suggest that GRP is involved in the multifactorial regulation of ACTH secretion.
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PMID:Gastrin-releasing peptide stimulation of corticotropin secretion in male rats. 131 54

The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH) in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT), 26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to 180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin-releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH-producing tumors. Some of these peptides were frequently found to be produced concomitantly with CRH. The results indicate IR-CRH to be produced by various neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare. The results also show that CRH-producing tumors produce multiple hormones.
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PMID:Production of immunoreactive corticotropin-releasing hormone in various neuroendocrine tumors. 135 72

Gastric acid secretion, gastrin-releasing peptide (GRP)-stimulated gastrin secretion and concentrations of somatostatin in gastric tissues were studied in sucking pigs (n = 48). In addition, gastrin concentrations in plasma and antral tissue were measured in fetal and sucking pigs (n = 66) from 22 days before birth (93 days gestation) to 36 days of age. From 3 days of age littermate pairs were treated twice a day with either saline (n = 20) or adrenocorticotropin [ACTH (1-24); n = 20]. Pentagastrin-stimulated acid secretion per unit stomach weight was 39 +/- 7 mumol H+/g/h at 0-1 day, increased to 194 +/- 15 mumol H+/g/h at 5-7 days and plateaued. Antral gastrin concentration was 0.14 nmol/g 10 days before birth and increased to 2.7 nmol/g at 5 weeks of age. Plasma gastrin was 25 +/- 2 pmol/l at 22 days before birth, increased to 102 +/- 14 pmol/l at birth and decreased during the postnatal period. Somatostatin concentrations were higher in antral than fundic tissues (p < 0.05) and remained constant during the postnatal period. Increased levels of glucocorticoids in plasma following ACTH treatment had no effect on the studied parameters except that it reduced basal (p < 0.07) and GRP-stimulated (p < 0.05) plasma gastrin concentrations at 6-7 days of age. Development of acid secretion and its gastric regulatory peptides in the pig is different from that in the rat in that it occurs at an earlier age and does not appear to be greatly influenced by elevated glucocorticoid levels from 3 days after birth.
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PMID:Ontogeny of gastric function in the pig: acid secretion and the synthesis and secretion of gastrin. 136 63

Autonomic dysfunction is an increasingly recognized problem in aging animals and man. The pathologic changes that produce autonomic dysfunction in human aging are largely unknown; however, in experimental animal models specific pathologic changes have been found in selected sympathetic ganglia. To address whether similar neuropathologic changes occur in aging humans, the authors have examined paravertebral and prevertebral sympathetic ganglia from a series of 56 adult autopsied nondiabetic patients. They found significant, specific, age-related neuropathologic lesions in the prevertebral sympathetic superior mesenteric ganglia of autopsied patients. Markedly swollen dystrophic preterminal axons compressed or displaced the perikarya of principal sympathetic neurons. Ultrastructurally, these swollen presynaptic axons contained abundant disoriented neurofilaments surrounded by peripherally marginated dense core vesicles. Immunohistochemical studies demonstrated that dystrophic axons contained tyrosine hydroxylase and neuropeptide tyrosine (NPY)-like immunoreactivity but not other neuropeptides (VIP, substance P, gastrin-releasing peptide [GRP]/bombesin, met-enkephalin). Similar to the animal models of aging, lesions were much more frequent in the prevertebral superior mesenteric ganglia than in the paravertebral superior cervical ganglia. These studies demonstrate anatomic, peptidergic, and pathologic specificity in the aging human nervous system similar in many respects to that which the authors have described in experimental animal models. Neuroaxonal dystrophy in the sympathetic nervous system may underlie poorly understood alterations in clinical autonomic nervous system function that develop with age.
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PMID:Neuroaxonal dystrophy in aging human sympathetic ganglia. 169 57

Immunohistochemical methods were used to determine the localisation of immunoreactivities to a variety of antigens involved in neurotransmission in the myenteric plexus of the colon in the rat and mouse. The findings in the two species were closely similar. Five neuronal types have been identified. (i) The axons of extrinsic noradrenergic sympathetic neurons, immunoreactive for tyrosine hydroxylase, supply the ganglia and the circular muscle. (ii) Bombesin immunoreactive intrinsic neurons with unbeaded axons are largely confined to the ganglia and tracts of the plexus. These neurons probably contain gastrin-releasing peptide, which is the mammalian analogue of bombesin. (iii) Somatostatin immunoreactive intrinsic neurons have long, beaded axons within the myenteric plexus and also outside the plexus, between the longitudinal and circular muscle layers. (iv) Intrinsic neurons containing opioid peptides (beta-endorphin, met-enkephalin, leu-enkephalin), have beaded axons that cannot be traced for long distances. They contact all the cell bodies in the ganglia and extend also into the interganglionic tracts and the smooth muscle. (v) Substance P immunoreactive somata and axons are present throughout the myenteric plexus and provide dense innervation to the smooth muscle. Extrinsic substance P immunoreactive sensory axons are probably also present.
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PMID:An immunohistochemical study of the myenteric plexus of the colon in the rat and mouse. 170 22

The effect of bombesin on the activity of dopamine (DA) neurons comprising the nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophysial systems in the male rat was determined by measuring: (1) the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after administration of a decarboxylase inhibitor, and (2) the concentration of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in brain (striatum, nucleus accumbens, median eminence) and pituitary regions (intermediate and neural lobes) containing terminals of these neurons. Intracerebroventricular (i.c.v.) injection of bombesin caused a dose- and time-related increase in the activity of DA neurons projecting to the median eminence and intermediate lobe of the pituitary, and a corresponding decrease in the concentrations of prolactin and alpha-melanocyte-stimulating hormone (alpha MSH) in the plasma. In contrast, doses of bombesin up to 10 ng i.c.v. failed to alter the activity of DA neurons terminating in the striatum, nucleus accumbens or neural lobe of the pituitary gland. Equimolar doses of bombesin and gastrin-releasing peptide (GRP), a bombesin-like peptide, increased the concentrations of DOPAC in the median eminence and intermediate lobe of the pituitary, suggesting that GRP-preferring receptors may be responsible for the stimulatory effects of bombesin on DA neuronal activity in these regions. The results of these studies suggest that bombesin increases the activity of tuberoinfundibular and tuberohypophysial DA neurons projecting to the median eminence and intermediate lobe of the pituitary, respectively, and thereby inhibits the secretion of prolactin and alpha MSH.
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PMID:Activation of tuberoinfundibular and tuberohypophysial dopamine neurons following intracerebroventricular administration of bombesin. 177 50

The degradation of several bioactive peptides and proteins by purified human dipeptidyl peptidase IV is reported. It was hitherto unknown that human gastrin-releasing peptide, human chorionic gonadotropin, human pancreatic polypeptide, sheep prolactin, aprotinin, corticotropin-like intermediate lobe peptide and (Tyr-)melanostatin are substrates of this peptidase. Kinetic constants were determined for the degradation of a number of other natural peptides, including substance P, the degradation of which has been described earlier in a qualitative manner. Generally, small peptides are degraded much more rapidly than proteins. However, the Km-values seem to be independent of the peptide chain length. The influence of the action of dipeptidyl peptidase IV on the biological function of peptides and proteins is discussed.
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PMID:The degradation of bioactive peptides and proteins by dipeptidyl peptidase IV from human placenta. 198 12

An immunocytochemical analysis with 33 antisera was undertaken to investigate the localization of 25 different neurotransmitter-related antigens in the hypothalamic suprachiasmatic nucleus in the rat. To obtain estimates of relative densities of immunoreactive axons a stereological approach was used involving counting of intersections of immunoreactive axons with a superimposed semi-circle test grid. All neurotransmitter-related antigens found in perikarya within the suprachiasmatic nucleus, including those stained with antisera against bombesin, gastrin-releasing peptide, neurophysin, vasopressin, somatostatin, gamma-aminobutyrate, glutamate decarboxylase and vasoactive intestinal polypeptide were also found in axons within the nucleus. A greater number of these immunoreactive axons was found within the nucleus than in the adjacent anterior hypothalamus. The size of all immunoreactive axons in the suprachiasmatic nucleus was consistently small; immunoreactive axons were found ramifying widely in the nucleus, often ending with terminal boutons near perikarya immunoreactive for the same antigen. All neurotransmitter-related substances found in perikarya of the suprachiasmatic nucleus were also found in axons crossing over the midline to innervate the contralateral nucleus, providing an anatomical substrate for a high degree of communication between the paired nuclei. Axons immunoreactive for other putative transmitters including serotonin arising outside the nucleus were also found in high densities within the nucleus and crossing over the midline between the nuclei. Immunoreactivity for some transmitters was found in axons of similar densities within and outside the nucleus, including antisera against tyrosine hydroxylase; a small number of dopamine beta-hydroxylase and a few phenylethanolamine N-methyltransferase-immunoreactive axons were found in the SCN, suggesting that dopamine, norepinephrine and epinephrine may occur in a limited number of axons in the nucleus. Small numbers of axons immunoreactive with antisera raised against cholecystokinin, prolactin, substance P, thyrotropin-releasing hormone and choline acetyltransferase were found within the suprachiasmatic nucleus. Axons immunoreactive for luteinizing hormone-releasing hormone, adrenocorticotropic hormone, alpha-melanocyte-stimulating hormone and neurotensin were rarely found within the suprachiasmatic nucleus; axons immunoreactive for luteinizing hormone-releasing hormone, adrenocorticotropic hormone, cholecystokinin and tyrosine hydroxylase were found in both horizontal and coronal sections in the area between the left and right suprachiasmatic nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurotransmitters of the hypothalamic suprachiasmatic nucleus: immunocytochemical analysis of 25 neuronal antigens. 241 88

Current understanding of the phenomenon of ectopic hormone production is largely based on a histopathological and immunocytochemical analysis of peptide hormone secreting tumours arising in non-endocrine tissues. Recent advances in the study of gene regulation show that the tissue-specific expression of genes is a highly sophisticated process and is unlikely to be disturbed by a spontaneous event such as point mutation in DNA. Study of several genes for frequently found ectopic hormones, i.e. prop-opiomelanocortin, vasopressin/neurophysin II, gastrin-releasing peptide, parathyroid hormone-related peptide, calcitonin gene-related peptide and beta-chorionic gonadotropin, suggests they are transcribed as they would be in their natural cell of origin. It is argued therefore that these data are compatible with the concept that the tumour cell of origin was capable of expressing these peptides, if only in a minor or transient manner. In one example, the ectopic ACTH syndrome, it is also necessary to explain the non-suppression of this gene's expression by elevated levels of glucocorticoids. Recent work suggests that this may result from physically present, but biologically inactive glucocorticoid receptors, a phenomenon that has occasionally been noted in hormonally inactive tumour tissue and cell lines.
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PMID:Ectopic hormone production. 247 14


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