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Biomedical subjects

J Ortego

Publications and source records attributed to J Ortego.

At least 19 recordsLinked to original sources
PubMed2003

Effect of exogenous administration of transforming growth factor-beta and famotidine on the healing of duodenal ulcer under the impact of indomethacin.

BACKGROUND: Non-steroidal anti-inflammatory drugs delay ulcer healing and cause refractory peptic ulcers in humans. OBJECTIVE: To study the effects of growth factors on experimental duodenal ulcer healing in indomethacin-treated rats. METHODS: Duodenal ulcers were induced in male Wistar rats by the serosal application of 75% acetic acid for 10 s. Rats were then treated with indomethacin (2 mg/kg/day; s.c.), transforming growth factor beta (15 ng locally injected subserosally at the ulcer site) or famotidine (5 mg/kg/day; p.o.), vehicle or combinations of treatments. On day 5, 8 or 12, rats were sacrificed and the ulcer area planimetrically measured under a dissecting microscope. Macroscopic area, microscopic diameter, collagen content and mucosal regeneration were assessed in histological preparations. Gastric secretion was assessed also in the pylorus-ligated rat-model. Data expressed as median and ranges were analyzed by non-parametric test. RESULTS: Indomethacin delayed ulcer healing but transforming growth factor-beta and famotidine improved ulcer healing and reversed the effects of indomethacin. Maximal differences were observed on day 8. Transforming growth factor-beta was associated with an increase in epithelial and granulation tissue cell proliferation. Famotidine induced a profound inhibition of gastric secretion and increased collagen secretion but it did not affect cell proliferation. CONCLUSIONS: Transforming growth factor-beta and famotidine accelerate ulcer healing delayed by indomethacin.

Animals↗
PubMed2002

Renin-angiotensin system expression and secretory function in cultured human ciliary body non-pigmented epithelium.

BACKGROUND: Renin-angiotensin system (RAS) components have been identified in human ciliary body and aqueous humour, pointing to a role for the RAS in the regulation of aqueous humour dynamics. Here, the authors examine the functional expression of a RAS and the effects of angiotensin II (AII) on a signal transduction pathway and ion secretion mechanism in cultured human ciliary body non-pigmented epithelium (HNPE). METHODS: RAS expression was examined in cultured HNPE cells using polymerase chain reaction (PCR) analysis. Secretory function was determined using spectrofluorescence imaging microscopy to measure cell calcium (Ca(2+)(I)) and volume responses. Single channel patch clamp techniques were employed to investigate ion channel activity. RESULTS: PCR analysis demonstrated the expression of angiotensinogen and the AT(1b) receptor in HNPE cells. A large conductance potassium (BK) channel (mean 190 (SEM 5.6) pS, n = 22 cells), was observed in plasma membrane patches. This channel was calcium sensitive with channel open probability (Po) increasing with increasing Ca(2+)(I) (K(0.5) 10.79 (0.44) microM Ca(2+), Hill coefficient of 1.04 (0.04)). AII (100 nM) increased the number (N) of active BK channels in HNPE cells and also the probability of channel opening (Po). N.P(o) increased from 0.008 (0.002) to 1.38 (0.4) following the addition of AII (p=0.0064). AII also induced a rapid rise in Ca(2+)(I) from resting values of 112 (14) nM to a peak of 992 (106) nM (p<10(-4)). A simultaneous cell volume reduction of 24.70% (3.34%) (p<10(-4)) occurred during this calcium signal. Losartan (1 microM) significantly blocked the AII induced BK channel activation (p=0.0131), the Ca(2+)(I) response (p<10(-4)), and the AII induced volume effect (p=0.0046). CONCLUSION: It was demonstrated that AII activates a Ca(2+)(I) signalling system which subsequently increases potassium ion channel activity. These effects are accompanied simultaneously by cell volume loss, indicating that AII acts as receptor operated secretagogue in HNPE cells. The ability of an AT(1) receptor antagonist to inhibit these processes may thus offer a new family of pharmaceutical agents to the current armamentarium in the treatment of glaucoma.

Angiotensin II↗
PubMed2001

Coronavirus derived expression systems.

Both helper dependent expression systems, based on two components, and single genomes constructed by targeted recombination, or by using infectious cDNA clones, have been developed. The sequences that regulate transcription have been characterized mainly using helper dependent expression systems and it will now be possible to validate them using single genomes. The genome of coronaviruses has been engineered by modification of the infectious cDNA leading to an efficient (>20 microg ml(-1)) and stable (>20 passages) expression of the foreign gene. The possibility of engineering the tissue and species tropism to target expression to different organs and animal species, including humans, increases the potential of coronaviruses as vectors. Thus, coronaviruses are promising virus vectors for vaccine development and, possibly, for gene therapy.

Coronavirus↗
PubMed2001

Superoxide anion and nitric oxide in high-grade esophagitis induced by acid and pepsin in rabbits.

It has been proposed that free radicals are involved in the pathogenesis of esophageal mucosal damage induced by acid and pepsin. Recent data have suggested that nitric oxide (NO) is involved in the mucosal defense of the esophagus and that superoxide anion plays a minor role in low-grade esophagitis. To study the role and potential interaction of NO and superoxide anion in an experimental model of high-grade esophagitis, acidified pepsin was perfused (45 min/12 hr) for five days in rabbits with different agents to modulate the generation of these radicals. Measurements included both macroscopic and microscopic mucosal damage, superoxide anion generation, NO synthase mucosal activity, and peroxynitrite formation. High-grade esophagitis was associated with mucosal superoxide anion generation. Treatment with exogenous superoxide dismutase completely prevented mucosal damage. The perfusion of acidified pepsin in the lumen of the esophagus was initially associated with increased NO synthase mucosal activity but decreased with the progression of damage. Generation of peroxynitrites was present in those cases with severe damage. Treatment with NO-modifying agents did not induce consistent modification of mucosal damage. It is concluded that superoxide anion is involved in the induction of high-grade esophagitis and that it interacts with nitric oxide to generate peroxynitrite radicals in this model. Superoxide dismutase but not NO-donor-modifying agents might have a therapeutic role in preventing severe esophageal mucosal damage induced by acid and pepsin.

Animals↗
PubMed2001

Diaphragm disease of the small bowel: a case without apparent nonsteroidal antiinflammatory drug use.

BACKGROUND: Diaphragm-like strictures of the small bowel are an infrequent complication of the treatment of patients with nonsteroidal antiinflammatory drugs (NSAIDs). STUDY: We report a patient with this condition in whom the use of NSAIDs was ruled out by both clinical history and objective blood testing of current aspirin use. RESULTS: He reported a history of recurrent episodes of colic abdominal pain during the past 25 years; he underwent three surgical operations for this condition. Before these symptoms, he had an undefined abdominal process with diarrhea, weight loss, and diffuse edema, which resolved spontaneously without reaching a diagnosis. CONCLUSIONS: We suggest that diaphragm-like strictures might be developed as a nonspecific response to different damaging insults to the intestine and are not necessarily associated with NSAID use.

Constriction, Pathologic↗
PubMed2001

Organization of two transmissible gastroenteritis coronavirus membrane protein topologies within the virion and core.

The difference in membrane (M) protein compositions between the transmissible gastroenteritis coronavirus (TGEV) virion and the core has been studied. The TGEV M protein adopts two topologies in the virus envelope, a Nexo-Cendo topology (with the amino terminus exposed to the virus surface and the carboxy terminus inside the virus particle) and a Nexo-Cexo topology (with both the amino and carboxy termini exposed to the virion surface). The existence of a population of M molecules adopting a Nexo-Cexo topology in the virion envelope was demonstrated by (i) immunopurification of (35)S-labeled TGEV virions using monoclonal antibodies (MAbs) specific for the M protein carboxy terminus (this immunopurification was inhibited only by deletion mutant M proteins that maintained an intact carboxy terminus), (ii) direct binding of M-specific MAbs to the virus surface, and (iii) mass spectrometry analysis of peptides released from trypsin-treated virions. Two-thirds of the total number of M protein molecules found in the virion were associated with the cores, and one-third was lost during core purification. MAbs specific for the M protein carboxy terminus were bound to native virions through the M protein in a Nexo-Cexo conformation, and these molecules were removed when the virus envelope was disrupted with NP-40 during virus core purification. All of the M protein was susceptible to N-glycosidase F treatment of the native virions, which indicates that all the M protein molecules are exposed to the virus surface. Cores purified from glycosidase-treated virions included M protein molecules that completely or partially lost the carbohydrate moiety, which strongly suggests that the M protein found in the cores was also exposed in the virus envelope and was not present exclusively in the virus interior. A TGEV virion structure integrating all the data is proposed. According to this working model, the TGEV virion consists of an internal core, made of the nucleocapsid and the carboxy terminus of the M protein, and the envelope, containing the spike (S) protein, the envelope (E) protein, and the M protein in two conformations. The two-thirds of the molecules that are in a Nexo-Cendo conformation (with their carboxy termini embedded within the virus core) interact with the internal core, and the remaining third of the molecules, whose carboxy termini are in a Nexo-Cexo conformation, are lost during virus core purification.

Amino Acid Sequence↗
PubMed2001

The membrane M protein carboxy terminus binds to transmissible gastroenteritis coronavirus core and contributes to core stability.

The architecture of transmissible gastroenteritis coronavirus includes three different structural levels, the envelope, an internal core, and the nucleocapsid that is released when the core is disrupted. Starting from purified virions, core structures have been reproducibly isolated as independent entities. The cores were stabilized at basic pH and by the presence of divalent cations, with Mg(2+) ions more effectively contributing to core stability. Core structures showed high resistance to different concentrations of detergents, reducing agents, and urea and low concentrations of monovalent ions (<200 mM). Cores were composed of the nucleoprotein, RNA, and the C domain of the membrane (M) protein. At high salt concentrations (200 to 300 mM), the M protein was no longer associated with the nucleocapsid, which resulted in destruction of the core structure. A specific ionic interaction between the M protein carboxy terminus and the nucleocapsid was demonstrated using three complementary approaches: (i) a binding assay performed between a collection of M protein amino acid substitution or deletion mutants and purified nucleocapsids that led to the identification of a 16-amino-acid (aa) domain (aa 237 to 252) as being responsible for binding the M protein to the nucleocapsid; (ii) the specific inhibition of this binding by monoclonal antibodies (MAbs) binding to a carboxy-terminal M protein domain close to the indicated peptide but not by MAbs specific for the M protein amino terminus; and (iii) a 26-residue peptide, including the predicted sequence (aa 237 to 252), which specifically inhibited the binding. Direct binding of the M protein to the nucleoprotein was predicted, since degradation of the exposed RNA by RNase treatment did not affect the binding. It is proposed that the M protein is embedded within the virus membrane and that the C region, exposed to the interior face of the virion in a population of these molecules, interacts with the nucleocapsid to which it is anchored, forming the core. Only the C region of the M protein is part of the core.

Amino Acid Sequence↗
PubMed2000

Thyroid autoantibodies in Thai type 1 diabetic patients: clinical significance and their relationship with glutamic acid decarboxylase antibodies.

OBJECTIVE: To study the clinical significance of thyroid autoantibodies in Thai patients with type 1 diabetes and their relationship with glutamic acid decarboxylase antibodies (GAD(65)Ab). METHODS: Thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab) were measured in 50 Thai type 1 diabetic patients. Forty-four patients also had GAD(65)Ab measured. Serum thyrotropin (TSH) was measured in all patients who had no history of thyroid disease regardless of thyroid antibody status. Clinical data including sex, age at onset and duration of diabetes, family history of diabetes, fasting c-peptide levels as well as frequencies of GAD(65)Ab were compared between patients with and without thyroid antibodies. GAD(65)Ab was also measured in 29 non-diabetic patients with hyperthyroid Graves' disease or Hashimoto thyroiditis as a control group. RESULTS: TG-Ab and TPO-Ab were positive in nine (18%) and 15 (30%) patients, respectively. Eight patients (16%) were positive for both antibodies. Two of 16 patients who were positive for TG-Ab or TPO-Ab had a previous history of hyperthyroidism prior to diabetes onset. Of the remainder, two were newly diagnosed with hyperthyroidism and one was found to have clinical hypothyroidism at the time of the study. None of 34 patients without thyroid antibodies had thyroid dysfunction. Eight patients with positive thyroid antibodies but without clinical thyroid dysfunction and 21 patients without thyroid antibodies were followed for up to 3 years, two patients of the first group developed hypothyroidism, whereas none of the latter developed thyroid dysfunction. The frequency of thyroid dysfunction at the time of initial study was significantly higher in patients with positive thyroid antibodies (3/14 vs. 0/34; P=0.021) and these patients who were initially euthyroid tended to have a higher risk of developing thyroid dysfunction (2/8 vs. 0/21; P=0.069). The frequency of thyroid antibodies was significantly increased in females and in those who had positive GAD(65)Ab. GAD(65)Ab was negative in all of the non-diabetic patients with autoimmune thyroid disease. CONCLUSIONS: About one-fourth of Thai patients with type 1 diabetes without thyroid disease had thyroid antibodies. The frequency of thyroid antibodies was increased in female and in GAD(65)Ab positive patients. The presence of thyroid antibodies is associated with a higher frequency of and may predict a higher risk for thyroid dysfunction in Thai type 1 diabetic patients.

Adult↗
PubMed2000

Nitric oxide and superoxide anion in low-grade esophagitis induced by acid and pepsin in rabbits.

It has been suggested that free radicals are involved in esophagitis. To study the role and potential interaction of superoxide anion and nitric oxide (NO) in low-grade esophagitis, we perfused acidified pepsin (30 min every 12 hr) for seven days in rabbits treated with different agents to modulate the generation of these radicals. Measurements included macroscopic and microscopic damage, superoxide anion generation, mucosal nitric oxide synthase activity, and peroxynitrite formation. Low-grade esophagitis was associated with increased nitric oxide synthase mucosal activity and mucosal damage was dose-dependently increased by treatment with the NO synthase inhibitor NG-nitro-L-arginine. Superoxide anion was scarcely generated in the mucosa, but this was not accompanied by any change in the activity of mucosal superoxide dismutase. Treatment with superoxide dismutase did not improve mucosal damage. Generation of peroxynitrites was not detected. In conclusion, nitric oxide is involved in the mucosal defense of the esophagus against acid- and pepsin-induced damage. Superoxide anion generation seems irrelevant in the induction of low-grade esophagitis and not sufficient to interact with nitric oxide to generate measurable mucosal peroxynitrite radicals.

Animals↗
PubMed2000

Clinical parameters (body mass index and age) are the best predictors for the need of insulin therapy during the first 18 months of diabetes mellitus in young adult patients.

To address the question whether there are simple clinical predictors of need for insulin in the first 18 months of treatment of diabetes presenting in young adult subjects, a prospective study of 24 patients with diabetes mellitus (age: 18-40 years) was designed. At diagnosis of diabetes, age, sex, body mass index (BMI), glycemia, ketonuria, C-peptide, insulin autoantibodies, islet cell antibodies and glutamic acid decarboxylase antibodies were recorded before starting any treatment. At the end of the follow-up (18 +/- 4 months), they were divided into two groups according to their need for insulin therapy: group 1 (n=15; 62%), who needed insulin therapy, and group 2 (n=9; 38%), who did not. Each marker was related to actual need for therapy necessity. Multivariate analysis showed that BMI and age were the variables with greatest predictive value regarding need for insulin. These data reveal that the need for insulin therapy in young adult diabetic patients may be supported by the clinical criteria of age and BMI, which are both easily and quickly determined.

Adolescent↗
PubMed2000

Expression of the TIGR gene in the iris, ciliary body, and trabecular meshwork of the human eye.

Mutations in the the glaucoma gene GCL1A, also known as trabecular meshwork glucocorticoid response (TIGR) or myocilin (Myoc), have been shown to be associated with juvenile-onset primary open-angle glaucoma. Very little is known about the pattern of expression of the TIGR gene in human ocular tissues. In-situ hybridization experiments demonstrated the localization of TIGR mRNA in cells throughout the iris, ciliary muscle, and the filtering portion of the trabecular meshwork of normal eye donors. The expression of TIGR protein was investigated by Western blot using an epitope-directed antibody to the carboxy terminus region of TIGR. This antibody was able to distinguish a recombinant TIGR fusion protein from a truncated TIGR form containing the naturally occurring Gln(368)-->stop mutation. In tissue extracts from the iris, ciliary body, and trabecular meshwork, the antibody recognized a major protein band of 57-kDa molecular mass. Deglycosylation treatment with PNGase F, NANase II, and O-glycosidase indicated that the 57-kDa protein in these tissues was unglycosylated. In agreement with this observation, in coupled in-vitro transcription/translation systems, the 57-kDa TIGR protein was unaffected by the presence of the processing and glycosylation activities of canine pancreatic microsomal membranes. These findings support the view that the expression of TIGR mRNA in cells of the iris, ciliary body, and trabecular meshwork correlates with that of TIGR protein, and that the 57-kDa TIGR protein was unglycosylated. These results, which are in contrast with earlier reports, raise the possibility that the TIGR protein might be processed into distinct forms in a tissue-specific manner.

Adult↗
PubMed2000

[Plasma levels of insulin and leptin in patients with morbid obesity and anorexia nervosa after weight loss or gain, respectively].

The present study was conducted in order to analyze the relationship existing between leptin and insulin levels in massive weight loss and weight recovery. Thirteen patients with severe obesity, 14 patients with anorexia nervosa and 13 healthy control subjects were studied. The patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet for 12 weeks. They were evaluated prior to (body mass index [BMI] 51.2 +/- 8.8 Kg/m2) and after drastic weight loss (BMI 40.6 +/- 6.7 Kg/m2). Patients with anorexia nervosa were treated exclusively with nutritional therapy during 12 weeks, and they were evaluated at their lowest weight status (BMI 16.2 +/- 2.2 Kg/m2) and after weight recovery (BMI 17.9 +/- 2.3 Kg/m2). The BMI of the normal subjects was in the normal range of 20 to 27 Kg/m2 (average 22.8 +/- 2.6 Kg/m2). BMI, percentage of body fat, waist circumference, and serum levels of leptin, insulin, and C-peptide were determined in each patient and normal subject. In severely obese patients, serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 51.8 +/- 22.3 to 23.7 +/- 10.2 ng/ml; insulin: from 27.1 +/- 13.3 to 17.2 +/- 7.2 mU/ml). In patients with anorexia nervosa, the mean serum leptin levels were significantly higher after weight recovery (5.5 +/- 3.2 vs 7.6 +/- 6 ng/ml). Serum leptin in the severe obesity group correlated positively with BMI, percentage body fat and waist circumference before and after weight loss. In those patients suffering from anorexia nervosa, serum leptin correlated positively with the BMI, percentage of body fat, and waist circumference in the low weight state and after weight recovery. In addition, their serum insulin correlated with BMI and waist circumference after weight recovery. These data reveal that serum leptin concentration correlates significantly with the BMI and body fat content 1) in subjects with a range of weight and caloric intake, 2) in obese patients after drastic weight loss; 3) in anorexic patients after weight gain; and that hyper- or normoinsulinemia do not seem to have any influence on the leptin changes caused by weight loss or gain.

Adipose Tissue↗
PubMed1999

Functional expression of components of the natriuretic peptide system in human ocular nonpigmented ciliary epithelial cells.

The expression of the natriuretic peptide system in the human ocular ciliary epithelium (CE) and in cultured nonpigmented (NPE) ciliary epithelial cells was examined. By RT-PCR and DNA sequencing, we demonstrated that the CE and NPE cells express mRNA for (i) ANP; (ii) BNP; (iii) NPR-A, NPR-B, and NPR-C receptors; and (iv) the neutral endopeptidase 24.11. Radioimmunoassay results indicate that BNP is secreted by cultured NPE cells at much higher levels than ANP. NPR-A and NPR-B receptors elicited a cGMP response to ANP, BNP, and CNP, in a rank order of potency (CNP >> ANP >/= BNP), indicative that the NPR-B receptor is predominant in NPE cells. A71915, an inhibitor of NPR-A activity, attenuated (65-75%) cGMP response to ANP and BNP, but not to CNP. C-ANP4-23 elicited an inhibitory effect (30-37%) on basal levels of cAMP in NPE cells and on forskolin NPE-treated cells, indicative that the NPR-C receptor is functional in these cells. PMA induced, in NPE cells, a long-term downregulation (75-85%) of NPR-C receptor mRNA, but not of NPR-A or NPR-B receptor mRNA, suggesting a differential regulation of NPR-C receptor mRNA via activation of PKC. Collectively, our data provide molecular evidence that all the components of the natriuretic peptide system with the exception of CNP are coexpressed in the ocular NPE ciliary epithelial cells, where they may function as local autocrine/paracrine modulators to influence eye pressure.

Atrial Natriuretic Factor↗
PubMed1999

Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis.

BACKGROUND & AIMS: The lack of appropriate animal models might explain the paucity of information on the mechanisms of mucosal damage and defense in reflux esophagitis. The aim of this study was to develop a model of esophagitis in rabbits mimicking human reflux esophagitis. METHODS: New Zealand white rabbits underwent surgery for placement of a plastic tube into the cervical esophagus. Acidified pepsin (AP) was intermittently perfused for different periods. Esophageal injury was assessed by macroscopic and microscopic examination, including the cell proliferation immunohistochemical parameter mib1. RESULTS: Rabbit losses (20%) were attributable mostly to postsurgical mortality and tube displacement. Perfusion of AP for 60 min/12 h or 45 min/12 h induced high-grade esophagitis by days 3 and 5, respectively, characterized by diffuse erosion/ulceration, inflammation, bleeding, and reactive epithelial changes. Perfusion of acidified pepsin for 60 min/day, especially at 30 min/12 h, induced low-grade esophagitis characterized by superficial epithelial loss, mild/absent inflammation, and epithelial reactive changes including increased cell proliferation, basal hyperplasia, and papillomatosis, which reached maximal expression by day 7. This perfusion regimen induced mucosal adaptation to damage. CONCLUSIONS: Different and highly reproducible esophageal mucosal lesions mimicking human reflux esophagitis can be induced in rabbits with repetitive acid and pepsin exposure.

Acute Disease↗
PubMed1999

Differential gene expression in the human ciliary epithelium.

The generation of expression and subtractive libraries from the ocular ciliary body and cultured ciliary epithelial cells has been instrumental in the cloning, identification and characterization of many genes which, overall reflect a representative profile of transcripts expressed in ciliary nonpigmented, ciliary pigmented and ciliary muscle cells. The cell-specific expression of some of these genes (i.e. a neurotrophic factor, a gene associated with juvenile open glaucoma, and a visual component) reveal a degree of cell differentiation with a diversity of functions and properties higher than previously thought. The protection from light-induced oxidative reactions, free radicals and detoxification, may be partially attributed to the high level of expression in the ciliary epithelium of antioxidative enzymes (i.e., glutathione S-transferase, glutathione peroxidases, selenoprotein-P). The expression of genes encoding plasma proteins (i.e., complement component C4, alpha2-macroglobulin, apolipoprotein D) is in contrast with the view that plasma proteins in aqueous humor are synthesized outside the eye (i.e., liver). The identification of neuropeptide-processing enzymes (i.e., prohormone convertases, carboxypeptidase E, peptidyl-glycine-alpha-amidating monoxigenase), neuropeptides (i.e., secretogranin II, neurotensin) and regulatory peptides (i.e., atrial natriuretic peptide and angiotensinogen) with hypertensive and hypotensive activities provide the molecular basis to support the view that the ciliary epithelium is a neuroepithelium with neuroendocrine functions. We propose a working model to demonstrate that aqueous humor and intraocular pressure are under neuroendocrine control through regulatory peptides synthesized and released by the ciliary epithelium and targeting the peptide producing cells at the inflow system by an autocrine mechanism and/or cells at the outflow system (i.e., trabecular meshwork cells) by a paracrine mechanism. Finally, we hypothesize that these mechanisms could be entrained in the light-dark cycle following the circadian rhythm of aqueous humor and intraocular pressure.

Ciliary Body↗
PubMed1998

Molecular identification and coexpression of galanin and GalR-1 galanin receptor in the human ocular ciliary epithelium: differential modulation of their expression by the activation of alpha2- and beta2-adrenergic receptors in cultured ciliary epithelial cells.

Here we report the coexpression of the neuropeptide galanin and GalR-1 galanin receptors in the human ciliary epithelium, a bilayer of neuroepithelial cells [nonpigmented (NPE) and pigmented (PE)] with neuroendocrine functions, and in a cell line (ODM-2) derived from the NPE cells. Stimulation of ODM-2 cells with phorbol ester [phorbol 12-myristate 13-acetate (PMA)] or forskolin resulted in an up-regulation (two- to threefold) of galanin mRNA expression. Procaterol, a selective beta2-adrenergic agonist, and the catecholamine isoproterenol exerted a long-term down-regulation on galanin mRNA expression when added alone or in combination with PMA or forskolin. These actions exerted by procaterol or isoproterenol were abolished in the presence of ICI 118,551, a selective beta2-adrenergic antagonist. A radioimmunoassay for galanin peptide indicated that galanin or a galanin-like product is present in the human aqueous humor fluid and is accumulated with time in the culture medium of ODM-2 cells. It is interesting that norepinephrine, which exhibited no effect on galanin mRNA expression, induced a down-regulation in the level of galanin or galanin-like product accumulated in the medium of cultured ODM-2 cells to levels even lower than those induced by beta2-adrenergic agonists. This effect is best explained by the concomitant up-regulation (four- to fivefold) of GalR-1 galanin receptor transcripts induced through the activation of alpha2-adrenergic receptors. These findings support the view that pathways elicited by the activation of alpha2- and beta2-adrenergic receptors influence the expression of galanin and GalR-1 galanin receptors in ciliary epithelial cells.

Adrenergic alpha-Agonists↗