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)

The secretion of peptide products derived from pro-ACTH/endorphin was examined with several radioimmunoassays and with polyacrylamide gel analyses of immunoprecipitates of radioactively labeled peptides. In studies using a mouse pituitary tumor cell line the accumulation of each of the four molecular forms of adrenocorticotropic hormone (ACTH) in tissue culture medium was shown to be a linear function of time. No evidence for self inhibition of secretion by accumulated, secreted peptides (i.e., ultra-short feedback) was found. Furthermore, synthetic human ACTH and synthetic camel beta-endorphin did not alter secretion of peptides when added to the culture medium at levels up to 10,000 times physiological. Stimulation of the release of ACTH-, endorphin-, lipotropin-, and 16k fragment immunoreactive material by norepinephrine was fully blocked by cobalt; by this criterion, stimulated release was calcium dependent. All the smaller molecules derived from the pro-ACTH/endorphin common precursor were secreted in equimolar amounts under all circumstances tested, within the precision of these studies (+/- 11%). Norepinephrine and cobalt did not significantly alter the secretion of pro-ACTH/endorphin and ACTH biosynthetic intermediate. The stimulation of secretion by norepinephrine and inhibition of secretion by cobalt was restricted to the lower molecular weight products derived from pro-ACTH/endorphin: glycosylated and nonglycosylated ACTH(1-39); beta-lipotropin, beta-endorphin, and gamma-lipotropin; and 16k fragment.
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PMID:Coordinate, equimolar secretion of smaller peptide products derived from pro-ACTH/endorphin by mouse pituitary tumor cells. 626 31

To study the relative roles of sodium (Na+) and calcium ions (Ca2+) in the response of adrenal glomerulosa cells, we investigated the effects of different Na+ concentrations in the incubation media and the actions of substances that interfere with Ca2+ fluxes. Basal aldosterone secretion and response to angiotensin II (AII), adrenocorticotropic hormone (ACTH), or potassium (K+) were dependent on extracellular Na+ concentration. Veratridine, a Na+ channel opener that dissipates Na+ gradients, blocked the stimulated steroidogenic response. Mersalyl acid and tetracaine, which are potent Ca2+ antagonists, blocked the effects of aldosterone secretagogues. Divalent cations with Ca2+ antagonistic action such as manganese M(n2+), nickel (Ni2+), and cobalt (Co2+) blocked the aldosterone secretory response to AII, ACTH, and K+. Barium (Ba2+) and strontium (Sr2+), known to mimick Ca2+ effects, increased or did not affect responses of the glomerulosa cells. Sodium vanadate, an inhibitor of ATP-dependent Ca2+ translocation, did not alter the stimulated aldosterone responses. Trifluoperazine (10(-6) M), an inhibitor of calmodulin, blocked AII and K+-induced aldosterone secretion, but was partially effective on ACTH-stimulated aldosterone output only at a concentration of 10(-5) M. The actions of ouabain on aldosterone biosynthesis were similarly affected by all these drugs. Thus, both extracellular Na+ and Ca2+ appear to play a role in the steroidogenic response of isolated glomerulosa cells. The intracellular action of Ca2+ may involve a calmodulin-like protein. The effects of ACTH are only partially dependent on Ca2+ as a second intracellular messenger.
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PMID:Relative roles of sodium and calcium ions in the steroidogenic response of isolated rate adrenal glomerulosa cells. 627 6

Recent amino acid sequence data suggest that trypsin-like and carboxypeptidase B-like activities are required for the processing of pituitary prohormones--e.g., pro-opiocortin (pro-adrenocorticotropin/lipotropin) and provasopressin in secretory granules. In this study the existence of a carboxypeptidase B activity in purified secretory granules from anterior, intermediate, and neural lobes of rat pituitary has been examined. A carboxypeptidase B activity that cleaved the COOH-terminal -Lys-Lys-Arg residues from the adrenocorticotropin fragment ACTH-(1-17) (a potential hormone product liberated from pro-opiocortin by a trypsin-like enzyme) was detected in anterior and intermediate lobe granules. A similar carboxypeptidase B activity was also present in purified secretory granules from rat pituitary neural lobes that cleaved the -Lys-Arg residues from [Arg8]vasopressin-Gly-Lys-Arg, a potential product cleaved from provasopressin. Secretory granule carboxypeptidase(s) from the three lobes of the pituitary was shown to cleave 125I-[Met]enkephalin-Arg6 to form 125I-[Met]enkephalin as well. 125I-[Met]Enkephalin was used as a model substrate for the quantitative assay of pituitary carboxypeptidase activity. The carboxypeptidase B in secretory granules from all three lobes was shown to be active at pH 5.5, but not at pH 7.4. Inhibition by the zinc metallocarboxypeptidase inhibitors guanidinopropylsuccinic acid, aminomercaptosuccinic acid, benzylsuccinic acid, 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, and the potato carboxypeptidase B inhibitor, and inhibition by the metal chelators EDTA and 1,10-phenanthroline demonstrate metal ion dependence of the pituitary granule carboxypeptidase activities. However, Co2+ stimulated the secretory granule carboxypeptidase B activities. Thiol protease inhibitors such as Cu2+ and p-chloromercuriphenylsulfonic acid also inhibited the activity. Thus, the secretory granule carboxypeptidase B-like activities in all three lobes of the pituitary appear to be similar thiol-metallopeptidases that differ from other carboxypeptidase activities previously described and may play an exclusive role in hormone biosynthesis in the pituitary.
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PMID:Carboxypeptidase B-like converting enzyme activity in secretory granules of rat pituitary. 632 44

Homogenates of rat neurointermediate lobes were purified by centrifugation on a Percoll gradient. Lysates of the Percoll gradient fractions were incubated with a synthetic octapeptide and pentapeptide substrate (N-acetyl Lys-Arg-Tyr-Asn-Leu-Thr-Ser-Val-amide and N-acetyl Lys-Arg-Tyr-Asn-Leu-amide), and enzymatic characteristics were compiled. Early assays on nonamidated forms revealed carboxypeptidase activity, whereas with the amide derivatives no carboxypeptidase activity could be detected. These amide substrates were therefore used in all subsequent incubations. High levels of a Leu/Thr and Lys/Arg cleavage were present in fractions almost throughout the Percoll gradient. Cleavages at Tyr/Asn, Thr/Ser, and Arg/Tyr were localized at different regions of the Percoll gradient. Surprisingly, none of the five enzymatic activities appear to be localized in the secretory granule fractions as defined by the presence of immunoreactive beta-endorphin in the gradient. All of the five proteolytic activities have a basic pH optimum (pH 8-9), and four of them seem to be thiol proteases, as categorized by inhibitor studies. The fifth one, namely the Try/Asn cleavage, is more likely to be due to a metalloendopeptidase, since it is activated by Zn2+ and Co2+.
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PMID:Subcellular fractionation of pituitary neurointermediate lobes: revelation of various basic proteases. 643 Jun 76

The electrophysiological properties of tumoral pituitary cells were studied in 4 types of human adenomas including prolactinomas, growth-hormone-secreting tumors, adrenocorticotropin-hormone-secreting adenoma and 'non-functioning' tumors. Only 9% of the cells from prolactinomas and ACTH tumors were excitable but they never elicited spontaneous action potentials. These cells did not respond to substances known to act on the hormone-releasing process (thyreoliberin, dopamine). However, 37% of the cells cultured from growth-hormone-secreting adenomas and from 'non-functioning' tumors displayed action potentials. The action potential was calcium-dependent, i.e., it was blocked by cobalt, nickel and methoxyverapamil and could be recorded in a sodium-free medium. Thyreoliberin triggered action potentials, whereas dopamine and gamma-aminobutyric acid inhibited electrical activity. These results show that human tumoral pituitary cells in culture are able to generate Ca2+-dependent action potentials. The data from growth-hormone-secreting tumors are in good agreement with the stimulus-secretion coupling concept; however, differences in the response of cells cultured from other types of human pituitary tumors suggest that each type of adenoma has specialized membrane properties.
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PMID:An electrophysiological study of cultured human pituitary cells. 681 48

Acid phosphatases of the rat ventral prostate were fractionated by gel filtration (GF) on Sepharose 6B, isoelectric focusing (IEF), and chromatofocusing (CF). In GF three activity peaks (GF-1, GF-2, GF-3) were disclosed. They showed some differences in substrate preference when six substrates (p-nitrophenyl phosphate; p-NPP; phenolphthalein phosphate, Phe-P; thymolphthalein phosphate, Tym-P; alpha-naphthyl phosphate, alpha-NP; beta-naphthyl phosphate, beta-NP; naphthol ASBI phosphate, N-ASBI-P) were tested. Differences were also encountered in their sensitivity to tartrate and fluoride. IEF gave seven bands at different pI values (8.3, 8.1, 7.9, 7.1, 6.4, 5.5, and 5.0) with alpha-NP and beta-NP but only four with N-ASBI-P. Four of the bands (8.3, 8.1, 7.9, 5.5) were sensitive to tartrate. In CF eight activity peaks (CF-1 to CF-8) were resolved with the six substrates. They differed from each other in pI values, pH optima, substrate preference, and modifier characteristics. Peaks CF-1 (pI 8.3, pH 5.5), CF-2 (pI 8.1, pH 4.2) and CF-3 (pI 7.9, pH 4.2) had a large substrate spectrum and high sensitivity to tartrate and fluoride. CF-4 (pI 7.1, pH 6.0) and CF-7 (pI 5.5, pH 4.2) were low in activity, preferred alpha-NP as substrate, and were moderately sensitive to tartrate. CF-5 (pI 6.4, pH 5.5) and CF-8 (pI 5.0, pH 5.0) were able to hydrolyse all substrates tested with moderate inhibition by tartrate. CF-6 (pI 6.0, pH 5.0) showed a relative preference for p-NPP and Phe-P with no hydrolysis of N-ASBI-P and Tym-P. Of these activities CF-6 and CF-7 were also clearly activated by Co2+. Peaks CF-6 and CF-7 appeared the most sensitive to p-chloromercuribenzoate. It is concluded that activities CF-1, CF-2, and CF-3 are lysosomal isoenzymes with minor structural differences. The others are possibly all nonlysosomal with greater biochemical differences. Some of them apparently represent the secretory form(s) of acid phosphatase in the rat ventral prostate.
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PMID:Separation of acid phosphatases in the rat ventral prostate by gel filtration, isoelectric focusing, and chromatofocusing. 683 62

An aminopeptidase with specificity directed toward peptides with acidic N-terminal amino acid residues has been isolated from mouse brain cytosol. Purification by ion-exchange chromatography and gel filtration resulted in an enzyme that hydrolyzed aspartyl-phenylalanine methyl ester at a rate of 13.2 mumols/min/mg protein at pH 7.5, an increase in specific activity of 1000-fold over that of brain homogenate. Its apparent molecular weight, determined by gel filtration, is approximately 450,000. Dipeptides with N-terminal aspartyl residues are cleaved preferentially to glutamic-containing analogs, and a neutral amino acid (or histidine) is necessary in the adjacent position. For peptides of the form aspartyl-X, relative activity was 100, 81, 71, 66, 19, or 0, where X was alanine, serine, leucine, phenylalanine, histidine, or proline, respectively. Tripeptides were more rapidly hydrolyzed than dipeptides; however, activity tended to decline with increasing chain length. The acidic aminopeptidase can account for almost all of the activity of brain cytosol toward the N-terminal aspartyl residue of angiotensin II, aspartyl-phenylalanine methyl ester or aspartyl-alanine, and the N-terminal glutamyl residue of adrenocorticotropin(5-10). The enzyme was unaffected by bestatin or amastatin. It was inhibited by o-phenanthroline and EDTA. The latter effect could be reversed completely by Zn2+ and partially by Mn2+ or Mg2+; Co2+ and Fe2+ had no effect; Ca2+ was inhibitory. These properties distinguish the brain acidic aminopeptidase from aminopeptidase A isolated from human serum or pig kidney and the aspartyl aminopeptidase of dog kidney.
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PMID:An aminopeptidase from mouse brain cytosol that cleaves N-terminal acidic amino acid residues. 685 30

Acid phosphatase activities were measured with five different substrates in the total homogenates as well as after gel filtration on Sepharose 6B and cellulose chromatography of bull, guinea pig, rabbit, and ram testes. The response of the hydrolysis rate to NaF (5 mmol/l), Co2+ (5 mmol/l) and Zn2+ (5 mmol/l) was also tested. In the total homogenate the hydrolysis of p-nitrophenyl phosphate was markedly activated by Co2+, while in the presence of Zn2+ an activation was recorded in guinea pig and some inhibition in the bull, rabbit, and ram testes. NaF caused a decline in the total acid phosphatase activity, particularly in guinea pig and ram. The gel filtration resulted in three separate activity peaks with p-NPP and beta-NP as substrates. N-ASBI-P, alpha-NP, and Tym-P gave only two peaks. After subsequent cellulose chromatography of the activities only peak II gave rise to two further activities. Peak I of gel filtration (enzyme I) was able to hydrolyze all substrates tested and was highly sensitive to NaF. Peak I of cellulose chromatography (enzyme II) also hydrolyzed p-NPP and beta-NP. It was rather resistant to NaF but sensitive to Zn2+. It was slightly activated by Co2+. Peak II of cellulose chromatography (enzyme IV) hydrolyzed only p-NPP and was markedly activated by Co2+ and Zn2+. The adult testes of bull, guinea pig, rabbit, and ram have a closely similar testicular acid phosphatase pattern. Due to relative differences in the concentrations of the four enzymes in the tissue, varying activity levels are recorded in the presence of different substrate and modifier combinations.
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PMID:Testicular acid phosphatases in cattle, sheep, guinea pig, and rabbit. 741 53

1. The actions of opioids on membrane properties of rat periaqueductal gray neurones were investigated using intracellular recordings from single neurones in brain slices. Morphological properties and anatomical location of each impaled neurone were characterized by use of intracellular staining with biocytin. The present paper primarily considers neurones which were directly hyperpolarized by opioids. The accompanying paper considers inhibition of synaptic transmission by opioids. 2. Met-enkephalin (10-30 microM) hyperpolarized 29% (38/130) of neurones. The hyperpolarization was fully antagonised by naloxone (1 microM, n = 3). The response to Met-enkephalin was not affected by agents which block synaptic neurotransmission (1 microM tetrodotoxin, and 0.1 microM tetrodotoxin + 4 mM Co2+, n = 3). 3. The specific mu-receptor agonist, D-ala-met-enkephalin-glyol (3 microM, n = 17) produced hyperpolarizations of similar amplitude to those produced by Met-enkephalin (10-30 microM). The EC50 of D-ala-met-enkephalin-glyol was 80 nM and the maximum response was achieved at 1-3 microM. The delta-receptor (D-Pen-D-Pen-enkephalin, 3 microM, n = 7) and kappa-receptor (U50488H, 3 microM, n = 5) agonists had no effect on the membrane properties of these neurones. 4. The opioid-induced hyperpolarization was associated with an increased potassium conductance. Hyperpolarizations were accompanied by a significant decrease in membrane resistance between -70 and -80 mV, and a significantly greater decrease between -110 and -140 mV (n = 16). Hyperpolarizations reversed polarity at -111 +/- 3 mV (n = 16), close to the expected equilibrium potential for potassium ions. The reversal potential of outward currents increased by 24 mV when the extracellular potassium concentration was raised from 2.5 to 6.5 mM, which is close to the value predicted by the Nernst equation (25 mV) for a potassium conductance.5. Resting inward rectification (reduced input resistance at potentials more negative than - 100 mV in the absence of opioids) was significantly greater in neurones which were hyperpolarized by opioids than in those which were not hyperpolarized. The amplitude of action potential after hyperpolarizations was significantly smaller in neurones which were hyperpolarized by opioids. Other membrane properties did not differ significantly between opioid-sensitive and -insensitive neurones.6. Neurones hyperpolarized by opioids were multipolar (58%), triangular (21%) or fusiform (5%) in shape with a soma diameter of 22 +/- 1 microm (n = 19, longest axis). Dendritic spread was in a large radiating pattern, usually in all directions, with axons usually originating from primary dendrites. The axons were usually branched and projected in several directions. Morphological properties did not differ significantly between opioid-sensitive and -insensitive neurones.7. Neurones hyperpolarized by opioids were located predominantly in the lateral periaqueductal gray,as well as in the more dorsal areas of the ventrolateral periaqueductal gray, whereas neurones not hyperpolarized by opioids were located in the more ventral areas of the ventrolateral periaqueductal gray.8. These studies demonstrate that opioids acting on micro-receptors increase potassium conductance in a sub-population of large neurones located predominantly in the lateral column of the periaqueductal gray. The neurones hyperpolarized by opioids could be involved in the antinociceptive actions of opioids, but might also be involved in other functions because a large proportion lie outside of the main'antinociceptive zone' of the periaqueductal gray. It is also unlikely that these neurones are GABAergic,suggesting that they might not participate in the postulated antinociceptive action of opioids mediated via disinhibition of neurones which project to the ventral medulla.
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PMID:Hyperpolarization by opioids acting on mu-receptors of a sub-population of rat periaqueductal gray neurones in vitro. 781 1

Arginine vasopressin (AVP) stimulates adrenocorticotropin (ACTH) release from pituitary corticotrophs by a mechanism dependent on extracellular calcium (Ca2+e). The involvement, in this response, of Ca2+ influx via L-type voltage sensitive Ca2+ channels (VSCC) was studied using cultured ovine anterior pituitary cells. Representatives of 3 chemically distinct classes of organic antagonists of L-type VSCC (methoxyverapamil (D600), nifedipine and diltiazem) and 2 inorganic blocking ions (Cd2+ and Co2+) were used. All of the blockers reduced AVP-stimulated ACTH release, but none caused complete inhibition. ACTH release in response to raised extracellular K+ concentration was also inhibited by these antagonists, with D600 and Cd2+ completely abolishing the response. These results indicate that there is a considerable, but not total, dependence on Ca2+ influx via L-type VSCC during the ACTH response to AVP in ovine corticotrophs.
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PMID:The effects of a chemically diverse range of calcium channel antagonists on the AVP-stimulated ACTH response in ovine corticotrophs. 795 9


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