Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 14 alcoholic men without evidence of liver damage. After two weeks of alcohol abstinence, the patients were divided into two groups of seven patients each. Hypothalamic-hypophysial, thyroid, and gonadal axis tests were done on group 1 patients before disulfiram administration, and the tests were later repeated while the patients were taking disulfiram. Group 2 patients had initial testing done while taking disulfiram and repeat testing after the drug was stopped. The following abnormalities were found and were not affected by disulfiram: lack of suppression of both growth hormone and glucagon with oral glucose intake, and lack of response of follicle-stimulating hormone after administration of synthetic gonadotropin-releasing hormone. After disulfiram administration, we noticed a blunted response of thyrotropin to thyrotropin-releasing hormone.
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PMID:Evaluation of the hypothalamic-hypophysial, thyroid, and gonadal axes before and after disulfiram administration in patients with chronic alcoholism. 305 25

Systemic absorption of polypeptides through eyes has been demonstrated in this study to provide an effective route of peptide administration as an alternate to parenteral administration. TRH at 0.0025% reached a plateau of blood concentration at 0.05 ng/ml in 60 min. and stayed high for at least 4 hrs, thereafter. In contrast, a therapeutic dose of TRH (15 micrograms/70 kg i.v.) could maintain a blood concentration of 0.07 ng/ml. At 1%, TRH reached a plateau of 26 ng/ml in 2 hrs. and persisted in the plateau for 10 hrs. thereafter. At 5%, TRH peaked at 138 ng/ml in 60 min. and then fell gradually to a steady state of 60 ng/ml in 9 hrs from the peak. Addition of peptidase inhibitors (Leu-Leu, 4 mM; Bestatin, 60 microM; and DL-Thiorphan 0.6 microM) did not affect the uptake of TRH into systemic circulation. LHRH showed entirely different kinetic of systemic absorption through eyes. The blood concentration never reached peak or plateau during 12 hrs. of experimental period. The blood concentration of LHRH increased steadily during experiments. With 0.0025%, 1% and 5% of LHRH, they reached final highest blood concentrations of 0.13 ng/ml, 45 ng/ml and 95 ng/ml, respectively. The therapeutic dose of LHRH (15 micrograms/70 kg i.v.) could maintain a blood concentration at 0.25-0.3 ng/ml which was slightly higher than that reached with 0.0025% of LHRH instilled into the eye. Addition of peptidase inhibitor (Leu-Leu, 5 mM) enhanced the absorption of LHRH into systemic circulation slightly but significantly. Glucagon behaved similarly as TRH except that the blood concentration remained high without falling at 5% dose level. These results suggest that topical instillation of peptide drugs into eyes is a workable method for administration of these peptide drugs.
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PMID:Systemic delivery of polypeptides with molecular weights of between 300 and 3500 through the eyes. 317 41

The pars distalis of the avian adenohypophysis consists of well-defined cephalic and caudal lobes which are distinct in their cellular constituents. Immunocytochemical investigations on the pituitary hormones of the pars distalis of the Japanese quail reveal five types of secretory cells, adenocorticotropin (ACTH) cells, prolactin (PRL) cells, thyroid-stimulating hormone (TSH) cells, growth hormone GH (STH) cells, and FSH/LH (gonadotropic) cells. The ACTH cells, TSH cells, and PRL cells are restricted to the cephalic lobe, and GH (STH) cells are confined to the caudal lobe, while FSH/LH cells are distributed throughout the cephalic and caudal lobes. The median eminence of birds has distinct anterior and posterior divisions, each with different neuronal components. The avian hypophysial portal vessels also consists of two groups, anterior and posterior. The peculiar arrangement and distribution of the avian hypophysial portal vessels are possibly related to the distribution of neuropeptides in the two divisions of the median eminence and to the cytological and functional differentiation of two lobes of the pars distalis. The localization of perikarya and fibers containing luteinizing hormone releasing hormone (LHRH), somatostatin, vasotocin, mesotocin, corticotropin-releasing factor (CRF), vasoactive intestinal polypeptide (VIP), glucagon, metenkephalin, and substance P in the hypothalamus and median eminence of the Japanese quail has been investigated by means of immunohistochemistry using antisera against the respective neuropeptides. LHRH-, somatostatin-, VIP-, met-enkephalin-, and substance P-immunoreactive fibers are localized in the external layer of the anterior and posterior divisions of the median eminence, while CRF- and vasotocin-reactive fibers are demonstrated only in the external layer of the anterior division of the median eminence. The metenkephalin fibers are thicker in the anterior median eminence but the substance P fibers are more abundant in the posterior division. Mesotocin fibers occur only in the internal layer of the median eminence and neural lobe.
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PMID:Immunohistochemistry of the hypothalamic neuropeptides and anterior pituitary cells in the Japanese quail. 608 43

The widespread occurrence of opioid peptides and their receptors in brain and periphery correlates with a variety of actions elicited by opioid agonists and antagonists on hormone secretion. Opioid actions on pituitary and pancreatic peptides are summarized in Table 1. In rats opioids stimulate ACTH and corticosterone secretion while an inhibition of ACTH and cortisol levels was observed in man. In both species, naloxone, an opiate antagonist, stimulates the release of ACTH suggesting a tonic suppression by endogenous opioids. In rats, a different stimulatory pathway must be assumed through which opiates can stimulate secretion of ACTH. Both types of action are probably mediated within the hypothalamus. LH is decreased by opioid agonists in many adult species while opiate antagonists elicit stimulatory effects, both apparently by modulating LHRH release. A tonic, and in females, a cyclic opioid control appears to participate in the regulation of gonadotropin secretion. Exogenous opiates potently stimulate PRL and GH secretion in many species. Opiate antagonists did not affect PRL or GH levels indicating absence of opioid control under basal conditions, while a decrease of both hormones by antagonists was seen after stimulation in particular situations. In rats, opiate antagonists decreased basal and stress-induced secretion of PRL. Data regarding TSH are quite contradictory. Both inhibitory and stimulatory effects have been described. Oxytocin and vasopressin release were inhibited by opioids at the posterior pituitary level. There is good evidence for an opioid inhibition of suckling-induced oxytocin release. Opioids also seem to play a role in the regulation of vasopressin under some conditions of water balance. The pancreatic hormones insulin and glucagon are elevated by opioids apparently by an action at the islet cells. Somatostatin, on the contrary, was inhibited. An effect of naloxone on pancreatic hormone release was observed after meals which contain opiate active substance. Whether opioids play a physiologic role in glucose homeostasis remains to be elucidated.
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PMID:Endocrine actions of opioids. 608 80

This article deals with the neuropeptides found in the eye and their actions. Substance P (SP) and VIP have been found in the anterior chamber of the eye. Here SP is localized in the sensory nerves of the sclera, cornea, iris, ciliary body and ciliary processes. It is supposed to be a sensory transmitter but can also be liberated by peripheral nerve endings as a response to various trauma. When this happens in the eye, for instance, after irritation of the Vth cranial nerve, SP causes an intense and long lasting miosis and may have some further actions as well. VIP has been demonstrated in nerves (probably cholinergic) of the posterior choroid and ciliary body. It is a potent vasodilator and may regulate choroideal blood flow. The retina is especially rich in different neuropeptides. SP, VIP, neurotensin, enkephalin, somatostatin, glucagon and gonadotropin-releasing hormone have all been demonstrated in the inner plexiform layer of the retina of various animal species. Specific information about the physiological role of retinal neuropeptides is still scarce but research is in progress. Considering the clinical significance of the new information about ocular neuropeptides, SP seems to be the most important substance. Recently a synthetic SP antagonist was reported to block the inflammatory response in the rabbit eye, which suggests a clinical use for this type of compounds.
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PMID:Ocular neuropeptides. 617 9

We have evaluated the responsiveness of hypocalcemic magnesium-deficient patients to ACTH, TRH, gonadotropin-releasing hormone, and glucagon as determined by the rise in serum cortisol, TSH, LH, and plasma cAMP concentrations, respectively. It was previously been shown that the hypocalcemia of magnesium deficiency is secondary to impaired secretion of parathyroid hormone (PTH) along with renal and skeletal resistance to the action of PTH. Since PTH secretion and action are though to be effected through the intermediary action of cAMP, and magnesium is a required cofactor for adenylate cyclase, defective generation of cAMP could account for the observed defects in PTH secretion and action. Other hormonal systems requiring the intermediary action of cAMP may be similarly affected by magnesium deficiency. The results of the present study, however, demonstrate normal responsiveness of the adrenal cortex, thyrotrophs, gonadotrophs, and liver to their respective trophic hormones in hypocalcemic magnesium-deficient patients. The reason why these responses are intact while PTH secretion and action are impaired is unknown but may be accounted for by differing magnesium requirements of the adenylate cyclase complex in these tissues.
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PMID:End-organ response to adrenocorticotropin, thyrotropin, gonadotropin-releasing hormone, and glucagon in hypocalcemic magnesium deficient patients. 627 86

The present experiments tested the ability of putative neurotransmitters and neuromodulators to regulate cyclic adenosine 3':5'-monophosphate (cAMP) levels in rat hippocampal slices. Slices from ovariectomized adult female rats were equilibrated for 1 hr and incubated for 20 min with various test compounds, and cAMP was extracted and quantified using a competitive protein-binding assay. Norepinephrine, adenosine, histamine, and prostaglandins E1 and E2 alpha, induced moderate (1.5- to 5-fold) increases in cellular cAMP, whereas dopamine, serotonin, prostaglandin F2 alpha, and glutamate were relatively ineffective. Most striking was the observation that vasoactive intestinal peptide (VIP) produced marked elevation (approximately 80-fold at 6 microM) of hippocampal slice cAMP content. In contrast, other peptides produced only 2-fold increased (glucagon, somatostatin) or no change in cellular cAMP levels (enkephalins, LHRH, ACTH analogue, arginine vasopressin). Significant elevations in cAMP were seen with VIP concentrations as low as 20 nM; the cAMP response was half-maximal at 1 microM VIP and maximized between 10 and 20 microM. At maximally effective concentrations, VIP was 86% as effective in increasing cAMP as maximal concentrations of forskolin, a compound which activates adenylate cyclase in most cell types. The cAMP response to 10 microM VIP was pronounced after a 1-min incubation (16-fold elevations) and was maximal at 30 min (140-fold elevation). When slices from other brain areas were compared, it was found that regions known to contain high levels of VIP (cerebral cortex) also responded to VIP treatment with 30- to 50-fold elevations in cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Activators of cyclic adenosine 3':5'-monophosphate accumulation in rat hippocampal slices: action of vasoactive intestinal peptide (VIP). 631 11

Reabsorption and/or degradation of proteins or peptides are functions of the proximal tubule. Large polypeptides or proteins are reabsorbed by luminal endocytosis and hydrolyzed by lysosomal enzymes. Our recent studies indicate that small linear peptides are hydrolyzed at the luminal membrane, with reabsorption of metabolites. The renal transport and hydrolysis of radiolabeled Al, All, BKN, oxytocin, glucagon, insulin, and LHRH were studied. Techniques for in vivo microinfusion of surface tubules in rats, arterial infusion in filtering and nonfiltering rat kidneys in vivo, and in vitro microperfusion of isolated rabbit nephron segments were used. Reabsorption of radiolabeled material was measured and the intact peptide or its metabolites were identified and quantified in urine, renal venous blood, bathing medium, and/or collection fluid. In addition, peptides were incubated in the presence of isolated renal membrane preparations to identify a probably cellular site of hydrolysis. The findings indicate that in proximal, but not distal tubules, radiolabeled Al, All, BKN, glucagon, and LHRH are hydrolyzed by brush border enzymes at the luminal membrane, followed by reabsorption of metabolites. In addition, it was found that, similar to the small intestine, the proximal tubule reabsorbed small peptide fragments, which were further degraded intracellurarly, In vivo inhibition studies with excess peptides revealed that hydrolysis is a more specific process than studies with excess peptides revealed that hydrolysis is a more specific process than reabsorption of metabolites. Large or small, complex peptides like insulin, oxytocin, or vasopressin that contain disulfide bridges are not hydrolyzed at the luminal brush border of the proximal tubule. In vivo sequestration and slow degradation of insulin by rat tubules suggest that this peptide is reabsorbed by endocytosis and degraded in lysosomes. Thus, as the molecular complexity or weight of a peptide increases, the mechanism for renal tubular degradation, instead of depending on luminal membrane hydrolysis, may primarily involve endocytosis and lysosomal digestion. This recently described mechanism for hydrolysis and transport of small linear peptides in the proximal nephron is characterized by having a high capacity and is analogous to membrane hydrolysis described for intestinal microvilli. The process may be biologically important to (1) conserve amino acids, (2) inactivate toxic peptides, and (3) help regulate circulating levels of peptide hormones.
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PMID:Renal tubular processing of small peptide hormones. 704 58

Sixteen peptides were injected intracerebroventricularly to test their effects on rectal temperature of rabbits in a thermoneutral environment. In initial tests 5 micrograms alpha-MSH, ACTH(1--24), oxytocin, vasopressin and glucagon altered body temperature while ACTH(1--10), cholecystokinin, contraceptive tetrapeptide, gastrin, insulin, interferon, leupeptin, LHRH, panhibin (somatostatin), and proctolin did not. Bombesin also altered body temperature but in no consistent direction. In further tests on the effective peptides 1.25--5.0 micrograms alpha-MSH and ACTH(1--24) produced dose-related decreases in rectal temperature as great as 1.0 degrees C. The same doses of oxytocin and glucagon produced small, prolonged hyperthermias which did not exceed 0.4 degrees C. Vasopressin caused rapid development of small increases in rectal temperature; temperature returned to normal in 2--3 hr. The results suggest that five of the peptides tested may have roles in central mediation of normal body temperature, hypothermia, hyperthermia and fever.
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PMID:Central administration of peptides alters thermoregulation in the rabbit. 724 7

We examined the function of hypothalamic-pituitary target gland axes in 88 cases with epidemic hemorrhagic fever (EHF). It was found that all the three endocrine axes i.e. hypothalamic-pituitary-adrenocortical axis, hypothalamic-pituitary-thyroid axis and hypothalamic- pituitary-gonadal axis showed some functional impairment. In acute phase there were increased plasma ACTH, FSH and LH levels, which might be attributed to stress reaction in EHF patients. Most cases showed low or weak response of TSH to TRH and delayed response of LH to LHRH; some of the cases did not respond to 1mg of glucagon. These manifestations might be related with poor reserve of anterior pituitary or to disordered regulation of endocrine axes. The increased plasma cortisol and estradiol and the decreased plasma T3, T4 as well as testosterone during acute phase may have important clinical significance. Hence we suggest that in any case glucocorticosteroids should not be abused and that in severe patients thyroxine and durabolin should be administered to improve immunity and hepato-renal function.
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PMID:[Functional changes of hypothalamic-pituitary target gland axes and their clinical significance]. 790 72


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