Unexpected beta adrenergic effects of the antitumor agent, cyclocytidine, on rat salivary glands.
In addition to its potent antileukemic properties, cyclocytidine has a sialogogue action that depends on stimulation of beta adrenergic ereceptors of salivary glands. Furthermore, when chronically administered (for 3 days), cyclocytidine caused enlargement of parotid and submaxillary glands and heart that resembled the hypertrophy caused by chronic isoproterenol administration. The salivas evoked by cyclocytidine also closely resembled those evoked by isoproterenol, and were extremely viscous, and high in K+, (121 plus or minus 5.6, for submaxillary, and 42 plus or minus 2.9, for parotid), low in flow rate (0.007 mg/min times mg) and parotid saliva contained high concentrations of amylase (805 plus or minus 33 mg/mg gland). Cyclocytidine also caused marked emptying of parotid gland amylase. The cyclocytidine-induced salivary flow and gland emptying of amylase were prevented for 90 min when propranolol (but not dibenzyline or atropine) was administered prior to injection of the cyclocytidine. In addition, when the superior cervical ganglion was acutely removed, administration of cyclocytidine elicited salivary flow from the denervated as well as the innervated glands. These findings suggest that cyclocytidine does not affect salivary glands through indirect central or ganglionic actions. Cyclocytidine action does not exclusively involve beta receptors, since even in the presence of propranolol, secretory flow was evident after 90 min but when dibenzyline was given with the propranolol, complete blockade of cyclocytidine-stimulated saliva was effected. The dominant effect is, however, a beta adrenergic one. The undesirable side effects of cyclocytidine (parotid pain, postural hypotension, and cardiac hypertrophy) probably stem chiefly from its beta adrenergic properties and might be eliminated (or at least modified) by administration of propranolol with the cyclocytidine.
D000318:Adrenergic beta-Agonists; D000681:Amylases / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D006332:Cardiomegaly / Q000139:chemically induced; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D003714:Denervation; D005260:Female; D005725:Ganglia, Autonomic / Q000502:physiology; D006984:Hypertrophy / Q000139:chemically induced; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010306:Parotid Gland; D010643:Phenoxybenzamine / Q000494:pharmacology; D011188:Potassium / Q000032:analysis; D011433:Propranolol / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D051381:Rats; D012463:Saliva / Q000032:analysis / Q000187:drug effects; D012466:Salivary Gland Diseases / Q000139:chemically induced; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D013363:Submandibular Gland
D000318:Adrenergic beta-Agonists; D000970:Antineoplastic Agents; D003561:Cytarabine; D010643:Phenoxybenzamine; D012313:RNA; D001285:Atropine; D004247:DNA; D011433:Propranolol; D000681:Amylases; D011188:Potassium