Inhibitory effects of SR 58611A on canine colonic motility: evidence for a role of beta 3-adrenoceptors.

1. In order to clarify whether atypical or beta 3-adrenoceptors can modulate canine colonic motility in vivo, we studied the effects of SR 58611A (a selective agonist for atypical beta-adrenoceptors) alone and after pretreatment with beta-adrenoceptor antagonists on colonic motility in the conscious dog. The gastrocolonic response (postprandial increase in motility) was monitored by means of electrodes and strain-gauge force transducers chronically implanted along the distal colon. In some experiments, heart rate was also measured. The possible role of beta 3-adrenoceptors in mediating the effects of SR 58611A was also tested in vitro in circular muscle strips taken from the canine distal colon. 2. Intravenous infusion of SR 58611A, ritodrine or isoprenaline at doses inducing the same degree of tachycardia inhibited the gastrocolonic response to a different extent, with SR 58611A and ritodrine being more effective than isoprenaline. 3. In a dose-response study, SR 58611A was more potent in inhibiting colonic motility than in inducing tachycardia: the ED35 values for inhibition of colonic motility and induction of tachycardia were 23 and 156 micrograms kg-1, i.v., respectively. 4. The inhibitory effect of SR 58611A 100 micrograms kg-1, i.v., on the gastrocolonic response was reversed by alprenolol (non-selective beta-adrenoceptor antagonist), but resistant to CGP 20712A (beta 1-adrenoceptor antagonist) or ICI 118551 (beta 2-adrenoceptor antagonist). 5. In vitro, SR 58611A concentration-dependently relaxed circular muscle strips, an effect that was competitively antagonized by alprenolol with a pA2 value of 7.1, but resistant to CGP 20712A (100 nM), ICI 118551 (100 nM) or tetrodotoxin (1 microM). 6. The present study provides strong functional evidence for a role of atypical or beta 3-adrenoceptors in the modulation of canine colonic motility both in vivo and in vitro by an inhibitory effect most likely at the smooth muscle level.

Effects of short-term administration of human chorionic gonadotropin on immune functions in cryptorchid children.

To delineate the effects of human chorionic gonadotropin (hCG) administration on immune responsiveness, immunological parameters including serum immunoglobulins, total and differential white blood cell count T and B lymphocyte membrane phenotype, in vitro, proliferative response to phytohaemagglutinin, Concanavalin A (ConA) and pokeweed mitogen were studied in 13 prepubertal cryptorchid boys before, during, and 3 months after hCG therapy. Before treatment, all the immunological parameters were normal except for an unexpected high percentage of T suppressor-cytotoxic cells (CD8+). During therapy, the absolute number of total peripheral blood lymphocytes, and that of total T-cells, T helper-inducer cells and of CD8+ subsets were diminished. The percentage of CD8+ cells and lymphocyte response to ConA decreased significantly and returned to normal after hCG withdrawal. The possible effects of long-term hCG treatment remain to be determined.

Relapsing eruptive psoriasis and immunological changes triggered by growth hormone therapy in a growth hormone-deficient girl.

A 9.8-year-old girl with growth hormone (GH) deficiency and concomitant chronic and localized psoriasis of the groins and axillae showed repeated and sudden relapse of eruptive psoriasis after GH treatment. The aggravating effect of GH and the improvement of the skin condition after withdrawal suggests, at least in this case, that GH plays a significant role in the pathogenesis of psoriasis.