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PubMed1994

Cysteamine potentiates entorhinal activation of dentate gyrus granule cells in rats.

A dense plexus of somatostatin-positive fibers and varicosities is observed in the outer two-thirds of the dentate gyrus molecular layer where the glutamatergic perforant path afferents from the entorhinal cortex terminate. To test for a functional interaction between these two pathways, we examined the effects of cysteamine, which enhances somatostatin release for a few hours after administration but produces subsequent depletion of somatostatin lasting several days, on perforant path evoked potentials recorded in the dentate gyrus. Cysteamine (50-400 mg/kg, IP) increased the population spike dose-dependently both in anesthetized and in awake rats, but the slope of the population excitatory postsynaptic potential (EPSP) was left unchanged or even decreased. The antidromic population spike evoked by mossy fiber stimulation was not changed by cysteamine. The change is thought to be due to the increase in slope of the EPSP-spike relationship. In the hippocampal slice preparation, a similar effect of the drug (1-5 mM) on dentate evoked potentials was observed, suggesting that cysteamine acts through its effects on somatostatin in the hippocampus itself. In chronically implanted awake animals, the perforant path population spike was increased 1 h after cysteamine but returned to the predrug level by 24 h when somatostatin seemed to be depleted. These results suggest that hippocampal somatostatin released by cysteamine potentiates the response of dentate granule cells to perforant path input, without directly affecting synaptic transmission or general cell excitability.

Anesthesia↗
PubMed1992

Parenchymal organ cystine depletion with long-term cysteamine therapy.

Nephropathic cystinosis is a lysosomal storage disorder characterized by renal failure, multisystem organ damage, and poor growth. Oral cysteamine therapy retards renal deterioration and enhances growth, but parenchymal organ cystine depletion has never been documented. We measured skeletal muscle cystine in 11 cystinosis patients not treated with cysteamine; analysis of their values plus 11 published values showed that muscle cystine increases linearly with age in cystinosis patients (slope, 0.074 nmol half-cystine/mg wet wt/year). In contrast, 15 patients treated for 4 to 11 years with oral cysteamine had a relatively constant muscle cystine content (slope, 0.004 nmol half-cystine/mg wet wt/year). The treated patients' mean muscle cystine, 0.091 +/- 0.064 (SD) nmol half-cystine/mg wet wt, was significantly less (P < 0.001) than that for the 11 youngest untreated patients, 0.754 +/- 0.534 nmol half-cystine/mg wet wt. On postmortem examination, a 9-year-old cystinosis patient treated for 8 years with oral cysteamine had liver, kidney, pancreas, lung, and spleen cystine values 5 to 90 times lower than those of an untreated age-matched control. We conclude that long-term oral cysteamine therapy routinely depletes cystinotic skeletal muscle of cystine; cysteamine is the treatment of choice for the prevention of both renal and nonrenal complications of cystinosis.

Adolescent↗
PubMed2003

Effect of cysteamine on redox-sensitive thiol-containing proteins in the duodenal mucosa.

Recent studies from our laboratory demonstrated that Egr-1 is upregulated in the rat duodenal mucosa during cysteamine-induced duodenal ulceration and that antisense egr-1 oligonucleotide aggravates the duodenal ulcers. This study was aimed to determine the effects of cysteamine on redox-sensitive Egr-1 transcriptional activity and on other thiol-containing proteins such as redox factor-1 (Ref-1) and thioredoxin (Trx). Here we demonstrate for the first time that cysteamine increases the expression and nuclear translocation of Egr-1, Ref-1, and Trx, and activates binding of Egr-1 to DNA. Moreover, we also show that Egr-1 forms a complex with other redox-sensitive transcription factors (e.g., AP-1, AP-2, NFATc, Sp1, PAX-5, MTF-1, c-Myb, and CREB) in rat duodenal mucosa and that cysteamine enhances the formation of these complexes. The antioxidant ebselen markedly elevated the nuclear Ref-1 expression and Egr-1/DNA binding, and decreased the ulcerogenic effect of cysteamine as did catalase. Thus, redox-sensitive signaling systems seem to play an important role in cysteamine-induced duodenal ulceration.

Animals↗
PubMed2003

Different effect of antiulcer agents on rat cysteamine-induced duodenal ulcer after sialoadenectomy, but not gastrectomy.

The focus was on salivary glands in cysteamine-induced duodenal ulcer and the different effects of antiulcer agents on cysteamine-induced duodenal ulcer in sialoadenectomized but not gastrectomized rats. We tested antiulcer agents on cysteamine-induced duodenal ulcer in rats (agents/kg i.p.) simultaneously with cysteamine 400 mg/kg s.c., rat killed 24 h thereafter subjected to no surgery (normal), to gastrectomy (24 h before) or sialoadenectomy, acute (24 h before) or chronic (21 days before). (i) Ulcerogenesis: cysteamine-induced duodenal ulcer had the same severity and incidence in normal, gastrectomized or acutely or chronically sialoadenectomized rats. (ii) Antiulcer effect under normal conditions or following gastrectomy: in normal or gastrectomized rats all agents tested, gastric pentadecapeptide BPC 157 [currently in clinical trials for inflammatory bowel disease (PL-10, PLD-116, PL-14736, Pliva) (10.0 microg or 10.0 ng), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg)] inhibited cysteamine-induced duodenal ulcers, acting through gastric acid-independent mechanisms. Following sialoadenectomy, acute or chronic: ranitidine, omeprazole and atropine were completely ineffective, while pentadecapeptide BPC 157 could protect. Thus, we found that contrary to stomach, salivary glands are implicated in cytoprotective agent activity (standard agents were ineffective after sialoadenectomy). Also, gastric pentadecapeptide BPC 157 was consistently associated with a cytoprotective effect, suggesting a beneficial activity distinctive from that of H2-receptor blockers, proton-pump inhibitors and anticholinergics; but probably replacing missing salivary glands factors.

Animals↗
PubMed1984

Comparative studies with somatostatin and cysteamine in different behavioral tests on rats.

In the present study the effects of somatostatin and cysteamine (a selective decreaser of the somatostatin level in the body) were compared in different behavioral tests on rats. Somatostatin inhibited the extinction of active avoidance behavior 8 hr and 24 hr after intracerebroventricular (ICV) treatment, while cysteamine facilitated it 4 hr and 8 hr after subcutaneous (SC) treatment. Somatostatin did not significantly influence the cysteamine-induced facilitation of the extinction. Somatostatin did not have a significant effect on T-maze spatial discrimination learning and reverse learning, whereas cysteamine markedly attenuated the performance 4 hr (1st day) after treatment. Somatostatin in a dose of 4 micrograms (ICV) increased the locomotor activity 10 min after treatment, while cysteamine markedly decreased all parameters of the open-field test. These effects of the drug had disappeared 24 hr after treatment. If different doses of somatostatin (4 micrograms or 10 micrograms ICV) were administered to cysteamine-pretreated rats, the peptide did not modify the drug-induced changes in the open-field test. The data suggest that the brain somatostatin might have a physiological role in the organization of certain types of behavior.

Animals↗
PubMed2001

Thiolated polymers: synthesis and in vitro evaluation of polymer-cysteamine conjugates.

The purpose of the present study was to synthesize and characterize novel thiolated polymers. Mediated by a carbodiimide cysteamine was covalently linked to sodium carboxymethylcellulose (CMC) and polycarbophil (PCP). The resulting CMC-cysteamine conjugates displayed 77.9+/-6.7 and 365.1+/-8.7 micromol thiol groups per gram of polymer, whereas the PCP-cysteamine conjugates showed 26.3+/-1.9 and 122.7+/-3.8 micromol thiol groups per gram of polymer (mean+/-S.D.; n=3). In aqueous solutions above pH 5.0 both modified polymers were capable of forming inter- and/or intra-molecular disulfide bonds. The reaction velocity of this oxidation process was accelerated with a decrease in the proton concentration. The oxidation proceeded more rapidly within thiolated CMC than within thiolated PCP. Permeation studies carried out in Ussing-type chambers with freshly excised intestinal mucosa from guinea pigs utilizing sodium fluorescein as model drug for the paracellular uptake revealed an enhancement ratio (R=P(app) (conjugate)/P(app) (control)) of 1.15 and 1.41 (mean+/-S.D.; n=3) for the higher thiolated CMC-cysteamine (0.5%; m/v) and PCP-cysteamine conjugate (1.0%; m/v), respectively. The decrease in the transepithelial electrical resistance values was in good correlation with the enhancement ratios. Due to a high crosslinking tendency by the formation of disulfide bonds stabilizing drug carrier systems based on thiolated polymers and a permeation enhancing effect, CMC- and PCP-cysteamine conjugates represent promising excipients for the development of novel drug delivery systems.

Acrylic Resins↗
PubMedDate not supplied

Susceptibility of dopamine D5 receptor targeted mice to cysteamine.

BACKGROUND: Recently we demonstrated that gastric mucosa of rats can synthesize, store and release dopamine. Out of five different subtypes, mRNA of D5 (=D1b) dopamine receptor is very abundant in the gastric epithelium. D1 receptor selective dopamine agonists have been shown to protect against experimental gastro-duodenal lesions. AIMS: To test the hypothesis that protective effects of dopamine involve D5 receptors, mucosal lesions were induced in D5 receptor deficient (KO) and wild-type (WT) mice using cysteamine. Morphology and gastric acid secretion of D5 KO mice were also studied. METHODS: Single doses of 600 mg/kg, 300 mg/kg cysteamine or vehicle were administered subcutaneously to fasted animals. After 24 h, number and severity of gastro-duodenal lesions were analyzed. Basal and histamine-induced maximal gastric acid output were measured by a stomach-sac wash-through method. RESULTS: All the KOs in the 600 mg/kg cysteamine group died within 4 h showing symptoms of toxicity while three out of four WTs survived (P<0.05). Mortality after 300 mg/kg cysteamine was significantly higher in KOs versus the WTs: 6/14 versus 2/11, P<0.05. Gastric lesion-index was also significantly higher in KOs (median, middle quartile): four (3-9) versus 0 (0-0), P<0.05. Duodenal lesions did not develop from this single dose of cysteamine in either genotype. Basal and histamine-induced maximal gastric acid output were comparable in the two genotypes. CONCLUSIONS: This study demonstrates that loss of D5 receptor causes mucosal vulnerability and increased toxicity of cysteamine in genetically manipulated mice. Thus, D5 receptor subtype is indeed likely to be involved in protective effects of dopamine in the stomach.

Animals↗
PubMed1999

Detrimental effects of oestradiol on cysteamine-induced gastroduodenal ulceration in the female rat.

The actions of the female sex steroid, oestradiol on cysteamine-induced mucosal ulceration has been evaluated in female Wistar rats. Administration of cysteamine (400 mg x kg(-1), s.c.) provoked macroscopic gastroduodenal mucosal injury (assessed planimetrically) and an increase in microvascular permeability (assessed by the extravasation of radiolabeled albumin) in the stomach and duodenum, determined 24 h later. Ovariectomy (2 weeks before cysteamine) reduced gastroduodenal macroscopic injury, and albumin extravasation following cysteamine challenge. Administration of oestradiol (1-5 mg x kg(-1), as an i.m. depot 1 week before cysteamine) dose-dependently augmented gastric and duodenal macroscopic mucosal lesions and microvascular permeability provoked by cysteamine. These findings indicate that oestradiol can exacerbate gastroduodenal ulceration and microvascular injury.

Animals↗
PubMed2004

Cysteamine, glutathione and ionomycin treatments improve in vitro fertilization of prepubertal goat oocytes.

The aim of this study was to improve in vitro embryo development of prepubertal goat oocytes by studying the effect of adding cysteamine to in vitro maturation medium, glutathione (GSH) to in vitro fertilization medium and ionomycin to the sperm capacitation medium. In experiment 1, we analysed the effect of 1 mM GSH added to fertilization medium of oocytes matured with 400 microM cysteamine. The control group were oocytes without cysteamine and GSH. In experiment 2, oocytes matured and fertilized in the presence of 400 microM cysteamine and 1 mM GSH, respectively, were inseminated with spermatozoa treated with ionomycin or heparin. In experiment 1, the percentages of total and normal fertilized oocytes were significantly higher for oocytes supplemented with cysteamine and GSH (40.26% and 30.20%, respectively) than for oocytes from the control group (16.66%, and 10.61%, respectively). The percentage of total embryos obtained after 7 days of culture was significantly higher in the group supplemented with cysteamine and GSH (30.62%) than in the control group (8.09%). In experiment 2, percentages of total and normal fertilized oocytes were significantly higher for the group of spermatozoa capacitated with ionomycin (52.21% and 37.17%, respectively) than with heparin (38.62% and 28.35%, respectively). After 7 days of culture, total embryo rate was significantly higher in the group of sperm capacitated with ionomycin (44.91%) than with heparin (38.69%). However, the percentage of embryos developed to the blastocyst stage was not affected by any of the treatments studied.

Animals↗
PubMed2005

Coexistence of multiple conformations in cysteamine monolayers on Au(111).

The structural organization, catalytic function, and electronic properties of cysteamine monolayers on Au(111) have been addressed comprehensively by voltammetry, in situ scanning tunneling microscopy (STM) in anaerobic environment, and a priori molecular dynamics (MD) simulation and STM image simulation. Two sets of voltammetric signals are observed. One peak at -(0.65-0.70) V (SCE) is caused by reductive desorption of cysteamine. The other signal, at -(0.25-0.40) V consists of a peak doublet. The pH dependence of the latter suggests that the origin is catalytic dihydrogen evolution. The doublet feature is indicative of two distinct cysteamine configurations. Cysteamine monolayer formation from initial nucleation to a highly ordered phase has been successfully observed in real time using oxygen-free in situ STM. Random cellular patterns, disordered adlayer formation accompanied by high step edge mobility, and ultimately a highly ordered (square root 3 x 4) R30 degrees lattice are observed sequentially. Pits are formed due to enclosure of the mobile edges during the adsorption process. In the highly ordered cysteamine layer, each unit has two spots with apparent 0.6 A height difference in STM images. The coverage 5.7 +/- 0.1 x 10(-10) mol cm(-2) determined by voltammetry supports that the spots represent two individual cysteamine molecules. A priori MD and density functional simulations hold other clues to the image interpretation and indicate that the NH(3)(+) groups dominate the tunneling contrast. A wide range of interface structures, showing variations in the sulfur binding site and orientation, gauche and trans conformers, and especially hydrogen-bonding interactions, are examined, from which it is concluded that the adsorbate structure is controlled by interactions with the solvent rather than with the substrate.

Computer Simulation↗
PubMed2003

Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients.

AIMS: Cysteamine is used to reduce tissue cystine content in patients suffering from nephropathic cystinosis. The objectives of the current study were to investigate pharmacokinetics and pharmacodynamics of cysteamine bitartrate in children and young adults with nephropathic cystinosis. METHODS: Cysteamine bitartrate was administered to 11 cystinosis patients at their regular dose level in a single-dose, open-label, steady-state study. Blood samples were collected and analysed for plasma cysteamine and white blood cell cystine content and pharmacokinetic and pharmacodynamic parameters estimated by NONMEM analysis using a linked pharmacokinetic-pharmacodynamic model. RESULTS: Cysteamine was rapidly cleared from the plasma (mean CL/F = 32.3 ml min(-1) kg(-1), range = 17.3-52.2), appeared to be extensively distributed (mean Vss/F = 15.1 l, range 2.7-32.3) and exhibited a mean Tmax of 1.4 h. White blood cell cystine content post-dosing was significantly decreased compared with pre- and post-dose values (average decrement approximately 47%). A counter-clockwise hysteresis was noted in all patients, suggestive of a lag time (mean Tlag = 0.44 h, range 0.22-0.92) between drug concentration and effect. CONCLUSIONS: The results of this study establish that cysteamine is rapidly cleared from the plasma but that an every 6 h dosing interval adequately maintains white blood cell cystine content below the target of 1 nmol cystine per mg protein.

Adolescent↗
PubMed2003

The evaluation and treatment of gastrointestinal disease in children with cystinosis receiving cysteamine.

OBJECTIVES: Cysteamine prevents organ damage in children with cystinosis, but may cause gastrointestinal (GI) symptoms. In this study we evaluated the nature of GI disease, and the value of omeprazole in controlling GI symptoms in these children. STUDY DESIGN: Upper GI disease was evaluated with endoscopy, gastrin levels, and acid secretion studies after oral administration of cysteamine, before and after 16 weeks of therapy with omeprazole. A symptom score was devised. RESULTS: Eleven children (mean age, 5.7 years) were studied. After cysteamine ingestion, before and after omeprazole therapy, the mean maximum acid output was significantly higher than the mean basal acid output. The maximum acid output was measured within 60 minutes of cysteamine ingestion and was reduced by omeprazole therapy (P<.01). The mean peak gastrin level was 30 minutes postcysteamine and was higher than baseline (P<.01). The initial mean symptom score (maximum score, 14) was 6.9 and fell to 0.7 (P<.0001) after 16 weeks of omeprazole therapy. At endoscopy, two children had diffuse gastric nodularity, and nearly all had cystine crystal deposits. CONCLUSIONS: GI symptoms in children with cystinosis receiving cysteamine are often acid-mediated and improve with omeprazole. Cystine crystals were detected in the GI tract and may signify inadequate treatment with cysteamine.

Anti-Ulcer Agents↗
PubMed1988

Effects of systemic and intracerebroventricular cysteamine on dexamethasone-induced suppression of corticosterone levels in the rat.

To investigate whether somatostatin systems plays a significant role in the regulation of the hypothalamic-pituitary-adrenal axis, the effects of cysteamine, a drug which reduces somatostatin levels, on the dexamethasone-induced suppression of plasma corticosterone levels were examined in the rat. Male Long Evans rats were handled daily for 1 week prior to receiving a standard dexamethasone suppression test. On the 1st day, rats received a 9.00 a.m. saline injection and blood samples were taken from the tail at 1.00 p.m. On the 2nd day, rats received dexamethasone or saline at 9.00 a.m. and a second blood sample was taken at 1.00 p.m. Experimental groups were pretreated with systemic injections of cysteamine, 5 min or 14 h, prior to receiving dexamethasone. Additional groups, previously implanted with guide cannulae, were given an infusion of cysteamine or saline into the lateral ventricle 14 h prior to dexamethasone. Circulating corticosterone levels were determined by radioimmunoassay. Rats were sacrificed immediately following each experiment and the hypothalamus dissected and assayed for levels of somatostatin immunoreactivity. The results of the first experiment showed that dexamethasone (10 micrograms/kg) alone reduced plasma corticosterone levels from control values (174 +/- 36 ng/ml) to undetectable levels (less than 25 ng/ml). Pretreatment with cysteamine 5 min prior to dexamethasone, while having no significant effect on basal corticosterone levels, completely blocked the dexamethasone-induced suppression of corticosterone levels. Similar observations were obtained with rats pretreated with cysteamine 14 h prior to dexamethasone. In contrast, intracerebroventricular cysteamine pretreatment did not block the dexamethasone-induced suppression of corticosterone levels. These results add further evidence in support of an involvement of somatostatin systems in the regulation of the hypothalamic-pituitary-adrenal axis.

Animals↗
PubMed1990

Examination of the potential antiulcer activity of the calcium antagonist propyl-methylenedioxyindene. III. Lack of effect on cysteamine-induced duodenal ulcers in rats.

Since propyl-methylenedioxyindene (pr-MDI) exhibits significant protective effects against stress-induced ulcers in rats at subcardiovascular doses (10-30 mg/kg, i.p.), the aim of the present study was to explore the effect of this intracellular calcium antagonist on cysteamine-induced duodenal ulcers at the same low doses. Duodenal ulcers were induced in rats with a single dose of cysteamine (425 mg/kg, s.c.), which produced an 80% ulcer incidence within 24 h without affecting gastric acid concentration. Administration of pr-MDI (10 and 30 mg/kg, i.p.) at 0, 6 and 12 h post-cysteamine did not afford protection against ulceration. On the other hand, atropine (10 mg/kg, s.c., administered at 0, 6 and 12 h post-cysteamine) resulted in a 69% inhibition of ulceration, and the antacid Maalox (2 ml, administered p.o. at 0, 2, 4, 6 and 12 h post-cysteamine) completely prevented ulceration. The failure of pr-MDI to protect against duodenal ulceration is discussed in relation to its pharmacological mechanism of action and the pathogenetic mechanism of action of cysteamine.

Aluminum Hydroxide↗
PubMed1992

Diamine oxidase activity in the duodenal mucosa of rats with cysteamine-induced ulceration.

Cysteamine administration to rats is followed by a high incidence of duodenal ulceration. The effect of cysteamine on the activity of diamine oxidase (DAO, histaminase) in the duodenal mucosa of the rat was investigated. Rats were injected subcutaneously with cysteamine on 2 successive days at doses of 10, 20 and 40 mg/100 g body weight and killed 24 h after the second dose. The results indicated that cysteamine at a dose of 40 mg/100 g body weight inhibited enzyme activity by about 27% (p less than 0.05). Lower doses of cysteamine did not significantly affect enzyme activity. In another experiment, rats were injected subcutaneously with either saline (control) or cysteamine at a single dose of 40 mg/100 g body weight and killed 4, 8, 12, 24, 48 and 60 h thereafter. The ulcerogen produced progressive reductions in enzyme activity, which were significant at 12 h (22% reduction) and 24 h (25% reduction). At 60 h, enzyme activity was not significantly different from that of control.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Functional and structural changes in the jejunum of the rat following cysteamine and stress-induced duodenal ulcer.

The effects of cysteamine and stress-induced duodenal ulcer on the functional and structural properties of the rat jejunum were investigated. The absorptive capacity of the jejunum was determined using alanine as the permeant solute and the single-pass perfusion technique. A statistically significant decrease (p < 0.01) in alanine absorption was observed after 8 h and 3 days of duodenal ulcer induction by stress and cysteamine respectively. However, alanine transport measured 7 days after cysteamine or stress ulcer induction showed no significant change from control values. Cysteamine and stress-induced duodenal ulcer did not show any significant change in water absorption across the jejunum when measured after 8 h, 3 and 7 days of ulcer induction. Microscopically, the jejunum of rats with 3-day cysteamine-induced ulcer exhibited diffuse type of apical derangements with excessive swelling of the villi and progressive degenerative changes. No such changes were noticed on the 7th day nor in the jejunum of the rats with stress-induced duodenal ulcer. The results suggest that cysteamine-induced duodenal ulcer produces an inhibition in the absorptive capacity of the jejunum which is time-dependent and reversible.

Alanine↗
PubMedDate not supplied

A cost-effectiveness analysis of the orphan drug cysteamine in the treatment of infantile cystinosis.

OBJECTIVE: Cysteamine is a recently licensed orphan drug used to treat the inherited metabolic disease cystinosis. The drug delays the onset of renal failure in cystinotic patients and may provide many other significant health benefits. This study examined the cost-effectiveness of the administration of cysteamine to cystinotic patients prior to end-stage renal disease (ESRD). METHOD: Decision-tree analysis and cost-effectiveness analysis. Cost data were estimated from current clinical charges and Medicare public-access reports. Life expectancy outcomes were derived from both published and unpublished clinical studies and from the U.S. Renal Data System. RESULTS: Cysteamine therapy can extend the life of kidneys and delay renal transplantation, thereby increasing life expectancy for patients with cystinosis. Patients receiving cysteamine therapy prior to renal failure have lifetime-treatment drug costs of $234,000, in comparison with $238,000 for those who are not medicated. Costs of cysteamine therapy are offset by savings associated with delaying transplantation and costs of dialysis. CONCLUSIONS: Use of the orphan drug cysteamine both improves health outcomes and reduces health care costs for patients with cystinosis.

Child↗
PubMed1985

Cysteamine causes reduction of prolactin monomers followed by aggregation in the rat pituitary gland.

Storage forms of PRL were studied in control and cysteamine-treated cultures of estradiol-induced tumors in Fischer 344 rats and in secretory granules isolated from these tumors to further investigate the mechanism of action of cysteamine on PRL. The two major bands visible when protein is stained after electrophoresis of isolated granules migrate to the position of PRL and GH monomers. Electrophoresis under reducing conditions changes the position, but does not noticeably increase the amount of each band. [3H]PRL in cells labeled for 8 h with [3H]leucine also exists predominantly as monomer. Immunoreactivity of PRL in cell lysates or isolated granules is not affected by incubation with reducing agents beta-mercaptoethanol or glutathione at concentrations up to 5 mM, but cysteamine decreases PRL immunoreactivity in isolated granules at concentrations of 3 mM and higher. Electrophoresis of isolated granules after incubation with 25 mM cysteamine for 1 h demonstrates that cysteamine converts PRL to the reduced form. After 4 h, or after dilution of the granules before solubilization, the amount of reduced monomer is decreased, and larger molecular weight species appear. The reduced monomer can be recovered by electrophoresis under reducing conditions. The fully immunoreactive form can be recovered by incubation for 1 h with dithiothreitol at concentrations of 0.3 mM-3 mM. These data indicate that: PRL exists predominantly in monomeric form in the rat pituitary gland, and cysteamine reduces PRL, and formation of disulfide-linked aggregates of PRL occurs subsequently under some conditions.

Animals↗