A comparative study of the effects of cyclocytidine and norepinephrine on renin and esterase release from mouse submandibular gland

Summary The effects of cyclocytidine and norepinephrine on the release of renin and esterase from mouse submandibular gland were compared in in vivo and in vitro experiments. Cyclocytidine (150 mg/kg i.p.) produced the depletion of renin and esterase in in vivo experiments as did the -adrenoceptor agonist norepinephrine (1 mg/kg i.v.). Cyclocytidine was more effective in depleting renin and esterase than norepinephrine. The -adrenoceptor antagonist phenoxybenzamine (10 mg/kg i.p.), but not the -adrenoceptor antagonist propranolol (10 mg/kg i.p.), attenuated the depletion of renin and esterase by both cyclocytidine and norepinephrine. These results suggest that the mechanism of action of cyclocytidine on the release of renin and esterase in mouse submandibular gland could be similar to that of norepinephrine, and the secretory process for both cyclocytidine and norepinephrine could be initiated by activation of -adrenoceptors. In in vitro experiments using dispersed cells, cyclocytidine (10^–7 M–10^–2 M) had no effect on renin and esterase release, but dose-dependent release of both was clearly observed in response to norepinephrine (10^–7 M–10^–4 M). Immunocytochemical studies of renin in both in vivo and in vitro preparations showed similar enzymatic activity as measured by radioimmunoassay. The results of in vitro experiments did not correspond to those of in vivo experiments, which may suggest that the site of action of cyclocytidine in mouse submandibular gland may be different than that of norepinephrine. Pretreatment with bretylium (20 mg/kg, i.p.) prior to i.p. injection of cyclocytidine (150 mg/kg) completely blocked the esterase depletion induced by cyclocytidine. From these results, it seems possible to conclude that the in vivo effect of cyclocytidine on mouse submandibular gland is an indirect one and is mediated via reflex activation of sympathetic nerves.