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)

A protein that inactivates the immunoreactivity of GnRH, TRH and angiotensin II has been isolated from human term placentae. Only in the presence of DTT, a sulphydryl agent, are OXY and SRIF also inactivated by this protein. However, it is without effect on CRF, hCS, or hCG. It also inhibits the biological activity of GnRH, i.e. its ability to stimulate pituitary LH and FSH. The ability of this protein to inactivate GnRH, TRH or angiotensin II can be inhibited by various peptidase inhibitors. Thus, we have postulated that it is a chorionic peptidase, specific for these peptides, and herein called chorionic peptidase-1 (C-ase-1). Isolation of this protein, C-ase-1, has been effected using permeation, ion exchange and affinity chromatography. As estimated by SDS-PAGE and HPLC analyses, C-ase-1 has an apparent molecular weight of 58,000. It is proposed that C-ase-1 may be an important chorionic regulator of GnRH, TRH and angiotensin II levels during pregnancy.
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PMID:Characterization and purification of a placental protein that inactivates GnRH, TRH and angiotensin II. 250 48

Culturing sympathetic ganglion neurons in vitro may modify phenotypic expression of some neurotransmitters. For dorsal root ganglia (DRG), contradictory results have been reported; most studies have used immature material. We have therefore performed a detailed immunocytochemical analysis of the transmitter content of cultured adult rat DRG neurons. To demonstrate possible modifications of neurotransmitter phenotypes, we have compared the results obtained with the same techniques on neurons cultured for 3 days and on freshly dissociated DRG cells. Also, the transmitter profile of cultured neurons was compared with that known from in situ studies. Out of 22 antigens studied, 20 were detected in cultured DRG neurons. All of them were expressed in small and/or intermediate-sized cells. Large neurons only contained CGRP, VIP, NPY, beta-END, ENK, and GABA. The percentage of immunostained neurons varied for the various antisera: less than 10% of cultured neurons were positive for ENK, beta-LPH, beta-END, DYN, VASO, and OXY; 10-30% for SOM, CCK, CAT, and SP; and greater than 30% for NPY, CRF, GLU, NT, VIP, GABA, GRP, CGRP, 5-HT, and TRH. In the latter two groups of transmitters (except CGRP), the proportion of immunoreactive neurons was by far larger in cultured than in freshly dissociated DRG. The most pronounced (greater than 25%) increase in the proportion of positively stained neurons after culturing was observed for the GRP, CRF, TRH, and 5-HT antisera. Serotonin was the only transmitter identified in cultured but not in freshly dissociated cells. These data indicate, on one hand, that various antigens, for example, CAT, GABA, NT, TRH, NPY, beta-LPH, and beta-END, which up to now have not been described in DRG in situ, can be detected immunocytochemically a few hours after dissociation of adult rat DRG. On the other hand, several transmitters, for example, VIP, NPY, SP, GABA, GLU, NT, GRP, CRF, TRH, and 5-HT, are expressed in a significantly higher proportion of cells in cultured than in freshly dissociated preparations. This might reflect a change in the phenotypic expression of transmitters due to the new environment generated by the culture conditions, a hypothesis that can be tested by measuring specific mRNA levels. Moreover, considering the plasticity and multipotentiality of their transmitter phenotype, cultured adult DRG neurons might represent an interesting material for autografts into the injured central nervous system.
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PMID:Neurotransmitter phenotype plasticity in cultured dissociated adult rat dorsal root ganglia: an immunocytochemical study. 256 40

GHRH receptors in pituitary adenoma cell membranes from five patients with acromegaly were characterized using [125I] [His1,Nle27]GHRH-(1-32)NH2 ([125I]GHRHa) as a ligand. Specific binding of [125I]GHRHa to adenoma cell membranes was maximal within 20 min at 24 C, remained stable for 60 min, and was reversible in the presence of 500 nmol/L human GHRH-(1-44)NH2 (hGHRH). The specific binding increased linearly with 10-160 micrograms cell membrane protein. This binding was inhibited by 10(-11)-10(-6) mol/L hGHRH in a dose-dependent manner, with an ID50 of 0.20 nmol/L, but not by 10(-7) mol/L vasoactive intestinal peptide, glucagon, somatostatin-14, somatostatin-28, TRH, LHRH, and CRH. The specific binding of [125I]GHRHa to the membranes was saturable, and Scatchard analysis of the data revealed an apparent single class of high affinity GHRH receptors in five adenomas from acromegalic patients; the mean dissociation constant was 0.30 +/- 0.07 (+/- SE) nmol/L, and the mean maximal binding capacity was 26.7 +/- 7.0 (+/- SE) fmol/mg protein. In three nonfunctioning pituitary adenomas, GHRH receptors were not detected. The plasma GH response to hGHRH (100 micrograms) injection was studied in four acromegalic patients before surgery. Plasma GH levels increased variably in response to hGHRH injection in all four patients. However, there was no correlation between the characteristics of the tumor GHRH receptors and plasma GH responsiveness in these patients. We conclude that pituitary GH-secreting adenomas have specific GHRH receptors. Exogenously administered GHRH presumably acts via these receptors, but the variations in plasma GH responsiveness to hGHRH in these patients cannot be directly related to the variations in binding characteristics of the GHRH receptors on the GH-secreting adenoma cells.
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PMID:Characterization of growth hormone-releasing hormone receptors in pituitary adenomas from patients with acromegaly. 283 73

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81

The pharmacokinetics and the endocrine profile of a new low molecular somatostatin derivative, SMS 201-995, were investigated in a group of 35 normal subjects. Clearance studies (n = 6) for this peptide showed a prolonged half-life in plasma, 113 min, following single sc injections of 50 or 100 micrograms. Arginine stimulation tests (n = 6) were conducted immediately and 180 min after sc injection of 50 micrograms of SMS 201-995. The stimulatory effect of arginine on GH and insulin was counteracted by the peptide at the P less than 0.001 and P less than 0.02 significance level, respectively. Delayed arginine stimulation revealed a persistent blockade of the GH release (P less than 0.02), whereas a recovery of the insulin response was observed. Plasma glucagon increments following a standard protein meal (n = 10) were significantly (P less than 0.001) inhibited by previous sc injection of 50 micrograms of SMS 202-995. Pretreatment with 50 and 100 micrograms of SMS 202-995 sc (n = 9) inhibited (P less than 0.001) the stimulatory effect of TRH (200 micrograms iv) on TSH without modifying basal levels. The injection of 100 micrograms/h during sleep completely abolished the nocturnal GH peak in 4 volunteers. No rebound rise after decline of the suppressive action on GH was recorded in any of the trials. Safety chemistries and blood coagulation studies remained normal and no side-effects or untoward reactions were recorded throughout the investigation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endocrine profile of a long-acting somatostatin derivative SMS 201-995. Study in normal volunteers following subcutaneous administration. 287 84

In order to compare the effects of somatostatin-28 (SS-28) with those of somatostatin-14 (SS-14) in humans, we administered both compounds randomly in 5 healthy persons and 3 patients with active acromegaly. Blood glucose, growth hormone, insulin, glucagon, TSH, FSH, LH and prolactin were estimated after arginine, TRH and LHRH stimulation in the normals and without stimulation in the acromegalics. Both substances were administered in doses of 25, 50, 200 and 250 micrograms. Our results indicate that SS-28 is at least 5 times more potent in man than SS-14 as far as inhibition of growth hormone, insulin, glucagon and prolactin secretion is concerned. On the other hand SS-28 is at least 2 times more potent than SS-14 in the inhibition of TSH, FSH and LH. If this difference in potency is calculated on the basis of equimolarity, the action of SS-28 becomes even much greater. According to these findings, SS-28 appears to be either the main hormone and SS-14 a fragment of it with a lesser degree of biologic activity, or the prohormone with special properties.
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PMID:Differences between somatostatin-28 and somatostatin-14 with respect to their biological effects in healthy humans and acromegalics. 288 Jun 90

Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 (SMS), at a dose of 50 micrograms sc twice daily in the first 2 weeks of treatment and 100 micrograms sc thereafter. Four h after the first injection of SMS, GH levels became normal in 8 of the 12 patients. Basal glucose levels were significantly lower at the 28th day of treatment. This glucose lowering effect was stronger in the diabetic than in the nondiabetic patients. The postprandial rise of insulin levels was reversed by SMS, leading to a more pronounced postprandial rise of glucose, whereas the postprandial secretion of glucagon was also reversed by SMS. The rise of glucose levels during oral glucose loading was similar before and during SMS, despite a strong inhibitory effect of the drug on the insulin rise after glucose loading. Basal TSH levels were not influenced by SMS, the TRH-induced TSH response, however, was significantly blunted. Although the basal PRL levels were significantly reduced by SMS, the TRH-induced PRL rise was similar before and during administration of the analogue. Paradoxical GH responses to TRH disappeared in 7 out of 8 patients during SMS. Paradoxical GH responses to GnRH, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. The GH response after GHRH administration was strongly suppressed by SMS. During long-term treatment (up to 2 years), the GH level obtained within 5 h after the last injection of SMS remained normal in the patients whose GH levels normalized at the first day of treatment. There was a good response of the disease to this treatment, and no serious adverse reactions were observed. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. The drug offers a new tool in the treatment of this disease.
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PMID:Long-term treatment of acromegaly with Sandostatin (SMS 201-995). Normalization of most anomalous growth hormone responses. 289 39

In order to know more about the secretory pattern of islet TRH in response to glucose and its possible physiological relevance, the release of this hormone as well as that of insulin, glucagon, and somatostatin was radioimmunologically measured. Whereas the secretion of immunoreactive insulin and somatostatin by incubated rat islets is known to be dose-dependently stimulated by glucose, that of glucagon and TRH was inhibited by glucose. Similarly, palmitate dose-dependently inhibited islet glucagon and TRH release. Exogenous TRH exerted strong and dose-dependent effects on islet secretion of the other hormones at the same concentration range at which its hypophysiotropic effects are produced (10(-10) to 10(-8) mol/l). It inhibited the insulin response to glucose and blocked that of glucagon, whereas it enhanced glucose-induced stimulation of somatostatin. These results are suggestive of a possible paracrine inhibitory role of islet TRH, either directly exerted on the secretion of insulin and glucagon or partially mediated through the stimulation of somatostatin release.
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PMID:Islet secretion of immunoreactive thyrotropin-releasing hormone and the 'paracrine-like' effects of its exogenous administration. 289 70

The effect of conditioned vs. fresh culture medium on the dopaminergic inhibition of TSH and PRL secretion by primary cultures of male rat anterior pituitary cells has been studied. In the presence of conditioned medium (that had been in contact with the cells over the 3-day culture period) 10(-6) M dopamine (DA) inhibited PRL secretion by 50% and TSH secretion by 30%. After 4 h of incubation with fresh medium 10(-6) M DA still inhibited PRL secretion by 50% but increased TSH release by 20%. TSH release was rapid and could be prevented by 10(-6) M prazosin, an alpha 1 adrenoreceptor antagonist. Fresh medium did not alter TRH induced TSH release. In parallel cultures and under identical conditions fresh medium reduced [3H]dihydroergocryptine (DHE) binding to DA receptors from 2.5 +/- 0.4 fmol/10(5) cells to 0.95 +/- 0.3 fmol/10(5) cells (means +/- SEM, n = 5, P less than 0.001). The effect of fresh medium was dose dependent against the dopaminergic inhibition of TSH secretion and against DA receptor binding. If 1 mU TSH was included, in fresh medium, the dopaminergic inhibition of TSH secretion remained unchanged and [3H]DHE binding to DA receptors did not fall. The rank order of potency of thyroid stimulators was bovine TSH (21 U/mg) greater than semipurified bovine TSH (Thytropar, 1.4 U/mg) greater than endogenous rat TSH (0.03 U/mg expressed as NIADDK-rat TSH-RP2) greater than Graves' immunoglobulin G (0.01 U/mg) when either DA or bromocriptine was used as the dopaminergic agonist. When anterior pituitary cells from hypothyroid rats were examined, the effects of culture medium on the dopaminergic inhibition of TSH and on DA receptor binding were approximately twice those observed in normal cells, but the inclusion of 1 mU TSH in the fresh medium completely prevented the loss of DA function and binding. PRL, human CG, ACTH, insulin, glucagon, and heat-inactivated TSH were unable to prevent the effect of medium replacement on dopaminergic inhibition of TSH and DA receptor binding. The data suggest a mechanism whereby TSH may control its own secretion via DA.
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PMID:Thyrotropin regulates thyrotroph responsiveness to dopamine in vitro. 300 10

Opiates stimulate the growth hormone and prolactin responses to stimuli in non-obese humans. Obese patients, however, show lowered growth hormone and prolactin responses and raised beta-endorphin levels. We therefore investigated the effect of the opiate antagonist naloxone on the stimulated growth hormone and prolactin secretions in a controlled double-blind study in obese patients. All patients received 200 micrograms TRH and 0.5 g/kg b.w. arginine together with 2 mg of naloxone or placebo i.v. in a randomized sequence. The TRH- and arginine-induced increases in prolactin and growth hormone were significantly greater after administration of naloxone (p less than 0.05). Naloxone also produced a significant increase in ACTH, cortisol and beta-endorphin when compared with placebo. TSH, triiodothyronine, thyroxine, insulin, glucagon and blood glucose showed no significant differences between both days of the trial. The effect of naloxone on growth hormone and prolactin secretions in obese humans can thus be regarded as a partial normalization. We therefore conclude that the hypothalamic regulatory disturbance of growth hormone and prolactin secretions in the obese could be caused by raised opiate levels.
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PMID:Naloxone increases the response of growth hormone and prolactin to stimuli in obese humans. 303 2


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