Inhibition of cyclocytidine-induced enlargement of parotid and heart by propranolol or sympathectomy.
Enlargement of salivary glands and heart of mouse as well as rat is caused by chronic administration of the antitumor agent cyclocytidine. In rat, the effects are maximal within 3 days, and are reversible, but with heart, not readily so. The organ enlargement, in both species, is the result of an action of the cyclocytidine involving beta adrenergic receptors since administration of propranolol 20 min prior to injection of cyclocytidine prevented the enlargement as well as the increases in nucleic acids associated with the enlargement. These beta adrenergic effects appear mediated through indirect actions of cyclocytidine that probably involve release of norepinephrine from postganglionic nerve fibers. This conclusion is based on the findings that parotid sympathectomized for 5 days does not exhibit the same secretory responses and glandular enlargement with cyclocytidine administration that are observed in the innervated mate. For example, amylase activity of the innervated gland was reduced from 525 mg/mg of gland (unstimulated parotid) to approximately 190 two hr after administration of 500 mg/kg of cyclocytidine, whereas that of the sympathectomized gland was unchanged (510 mg/mg). In addition, cyclocytidine caused only a small increase in weight and nucleic acid content of the sympathectomized parotid, whereas the innervated mate exhibited the usual marked increases in all parameters (weight and RNA were twice as great as those of untreated rats). Guanethidine and bretylium were used in conjunction with cyclocytidine to provide additional evidence for the indirect beta adrenergic action of cyclocytidine on heart and parotid gland.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003561:Cytarabine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology; D051379:Mice; D009929:Organ Size; D010306:Parotid Gland / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D013562:Sympathectomy
D000970:Antineoplastic Agents; D003561:Cytarabine; D011433:Propranolol