Calcium concentration of saliva and salivary glands of rat after cyclocytidine.

Cyclocytidine (CC), in addition to its antitumor properties, also causes copious flow of saliva. Calcium concentration of CC-evoked saliva from submaxillary (SM) and parotid (PA) glands of adult rats was initially 7 meq/liter and 15 meq/liter, respectively, and thus resembled that of sympathetically evoked secretion. From previous data, as well as present data, this is expected since CC apparently causes release of norepinephrine (NE) from adrenergic nerve endings. Present data also confirm that CC causes NE release since a single dose of reserpine (RES) (5 mg/kg), administered 24 hr prior to injection of CC in order to cause depletion of NE prevented the action of CC. Furthermore, the NE released by CC acts principally on beta-adrenergic receptors since propranolol administered prior to CC caused a marked reduction in flow and [Ca] of saliva, and prevented the usual CC-induced depletion of glandular calcium. An increase in [Ca] of SM but not PA gland was also caused by chronic (daily injections of 500 mg/kg body wt for 3 days) administration of CC. The same threefold increase was observed 2 days after injection of a single dose of CC also. The increase in glandular calcium was not prevented by propranolol, thus suggesting that this effect of CC on glandular [Ca] was probably not beta-mediated. The calcium increase may, however, be the result of depletion of NE. Thus, [Ca] of SM of CC-treated rats, that of RES-treated rats, and that of rats treated with RES + CC were very similar. If the mechanism of action of the two drugs were different (not NE depletion), the combined action of the two would have been additive.