Nicotinic and nonnicotinic receptor-mediated actions of vinblastine.

Vinblastine has been demonstrated to inhibit nicotinic acetylcholine receptor (nAChR) activity in adrenal chromaffin cells and superior cervical ganglia and to alter agonist binding affinity to nAChR of the electric organ of Torpedo californica. In cultured chromaffin cells, vinblastine (IC50, 8.9 microM) is significantly more potent than hexamethonium (IC50, 16 microM) and decamethonium (IC50, 18 microM) and significantly less potent than d-tubocurarine (IC50, 2 microM), pentolinium (IC50, 0.6 microM), and mecamylamine (IC50, 0.1 microM) in inhibiting nAChR-stimulated catecholamine release. These results demonstrate that vinblastine has moderately potent anti-nAChR activity on adrenal nAChR. On the other hand, vinblastine does not interfere with phrenic nerve stimulation of rat diaphragm musculature in concentrations up to 200 microM. However, in relatively high doses, vinblastine (10-200 microM) produces an increase in baseline tension of diaphragm muscle. This effect is concentration related (EC50, approximately 88 microM), reversible, and independent of phrenic nerve stimulation. The elevation in baseline tension is unaffected by nAChR blockade via d-tubocurarine, but is dependent upon the presence of extracellular calcium. The results suggest that vinblastine's antinicotinic actions are selective for neuronal-type nAChR and do not extend to nAChR of mammalian skeletal muscle. High concentrations of vinblastine appear to elicit contractures of skeletal muscle that are unrelated to nAChR.