naloxone and Hypertrophy

To elucidate the physiologic background that makes muscle hypertrophy, especially that due to strenuous exercise, often parallel to stress sensitivity and signs of acute phase immune response.. We used an animal model: lines of mice with hypertrophied (H) and normally developed (N) hind leg muscles, six in each case. Functional and receptor tests on cells from digested muscle tissue were made and analyzed by microplate cytofluorimetry and flow cytometry.. Higher percentages of cells with a phagocyte marker (> 2-fold) and with opioid (about 1.3-fold) receptors were found, whereas the portion of glucocorticoid receptor-bearing cells tended to differ only among H and N. Naloxone, an opioid receptor antagonist, failed only in H to exert a suppressive effect on dihydrorhodamine 123 oxidation.. These results and differences in responses of lipid trafficking and proteolytic activities to cortisol, naloxone and adrenergic receptor agonists suggest that not only the cell population associated with muscle tissue but also receptor-mediated responses that are known to be related to stress coping are different between H and N.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Animals; Epinephrine; Flow Cytometry; Glucocorticoids; Hindlimb; Hydrocortisone; Hypertrophy; Lipid Metabolism; Male; Mice; Muscle, Skeletal; Naloxone; Narcotic Antagonists; Narcotics; Norepinephrine; Oxidation-Reduction; Phagocytes; Receptors, Formyl Peptide; Receptors, Immunologic; Receptors, Peptide; Respiratory Burst; Rhodamines; Tetradecanoylphorbol Acetate

A rat model of infravesical outflow obstruction was modified to allow cystometric investigation in conscious, free-moving animals after intrathecal drug administration. The catheter position and extent of drug distribution were controlled by injection of dye and dissection of the spinal canal. Continuous cystometries were performed in awake normal rats as well as rats with bladder hypertrophy and hyperactivity following infravesical outflow obstruction. In some animals of each group, cystometry was performed with simultaneous recording of intra-abdominal pressure. The possible effects of the presence of the intrathecal catheter were studied, as well as the effects of saline, local anesthetics, morphine and naloxone administered through the catheter. Neither the presence of the intrathecal catheter nor injection of saline affected the cystometric pattern. Bupivacaine (50 micrograms) produced paralysis of both lower extremities and a complete, though reversible, suppression of micturition in normal rats. In rats with hypertrophy, intrathecal bupivacaine in doses of 50 micrograms and 100 micrograms produced decreases in micturition pressure, increases in bladder capacity and dribbling incontinence. However, the amplitude of spontaneous contractile activity increased after the administration. The inhibitory effects of morphine (0.5-10 micrograms) on micturition in normal rats, which were rapidly reversed by naloxone, were in accordance with results obtained in previous studies in anesthetized animals. Rats with bladder hypertrophy showed a similar response to morphine and naloxone. However, the bladder hyperactivity was not inhibited by morphine. We conclude that the present model seems reliable for the study of spinal mechanisms in the development of detrusor instability associated with infravesical outflow obstruction.

Topics: Animals; Bupivacaine; Disease Models, Animal; Female; Hypertrophy; Injections, Spinal; Morphine; Muscle Contraction; Muscle, Smooth; Naloxone; Rats; Rats, Sprague-Dawley; Spinal Cord; Urinary Bladder; Urinary Bladder Neck Obstruction

Intra-spinal cord injection of colchicine (2.5-5 micrograms/rat) produced an inhibition of reflex micturition leading to voiding suppression, bladder hypertrophy and overflow incontinence. Intraperitoneal administration of bremazocine, a kappa-receptor agonist with antagonistic properties for mu- and delta-receptors minimized the colchicine induced effects. The selective kappa-receptors agonist, U-69593, had little effect, while eledoisin or naloxone administration worsened rather than counteracted urine retention.

Topics: Analgesics; Animals; Benzeneacetamides; Benzomorphans; Colchicine; Eledoisin; Hypertrophy; Injections, Spinal; Naloxone; Pyrrolidines; Rats; Receptors, Opioid; Spinal Cord; Urinary Bladder; Urination

beta-Endorphin and other peptides derived from proopiomelanocortin are synthesized in testicular Leydig cells. To better understand the possible function of these and other endogenous opioid peptides in the testis, the opioid antagonists naloxone and nalmefene were administered intratesticularly to hemicastrated 5-day-old rats. Both naloxone and nalmefene potentiated testicular hypertrophy induced by unilateral orchidectomy at 11 days of age. Unexpectedly, at least a 100-fold lower dose of nalmefene was required to produce maximal hypertrophy than that previously reported for naloxone. Leydig and Sertoli cell functions were evaluated, respectively, by measurement of basal testosterone production in vitro and rat androgen-binding protein (rABP) in serum. The optimal dose of naloxone for hypertrophy (1 microgram/testis) suppressed testosterone production and had a nonuniform effect on rABP secretion (either had no effect or produced a slight increase). By contrast, the optimal dose of nalmefene for hypertrophy (0.01 microgram/testis) not only suppressed basal testosterone secretion, but also uniformly increased rABP levels in serum. Larger doses of this opioid antagonist, up to 1 microgram/testis, were not as effective on the three parameters measured (hypertrophy, testosterone secretion, and rABP levels). These results suggest that this agent has both antagonistic and agonistic activities in the testis. At the doses that produced optimal effects on hypertrophy, systemic administration of these antagonists produced no effects. The results of these studies suggest that intratesticular opiates exert a suppressive effect on Sertoli cell growth and rABP secretion. In addition, these peptides may modulate testosterone secretion by Leydig cells.

Topics: Androgen-Binding Protein; Animals; Animals, Newborn; Dose-Response Relationship, Drug; Endorphins; Hypertrophy; Leydig Cells; Male; Naloxone; Naltrexone; Orchiectomy; Rats; Rats, Inbred Strains; Sertoli Cells; Testis; Testosterone