Effects of Ca²⁺ and Calmodulin Antagonists on the Oxygen Uptake Induced by Acetylcholine or Substance P in Rat Submandibular Gland Slices

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Effects of Ca²⁺ and calmodulin antagonists on the oxygen uptake induced by acetylcholine (ACh) or substance P (SP) were investigated in rat submandibular gland slices. The oxygen uptake induced by ACh or SP was significantly inhibited by removing Ca²⁺ from the medium and the slices. The oxygen uptake by ACh in the Ca²⁺-deficient slices was almost completely recovered by the addition of 3.0 and 5.0 mM Ca²⁺, whereas that by SP was not recovered by the addition of 3.0 mM Ca²⁺, but recovered by 5.0 mM Ca²⁺. Ca²⁺ antagonists, diltiazem, verapamil and La³⁺, significantly inhibited the ACh-induced oxygen uptake. On the other hand, the SP-induced oxygen uptake was inhibited by diltiazem and La³⁺, but not by verapamil. Calmodulin antagonists, trifluoperazine, chlorpromazine and W-7, had no inhibitory effects on the ACh-induced oxygen uptake. The SP-induced oxygen uptake was not affected by trifluoperazine, chlorpromazine and low concentrations of W-7, but was inhibited by high concentrations of W-7. These results suggest that the ACh- or SP-induced oxygen uptake is dependent on the presence and permeability of Ca²⁺ with a subtle difference between the ACh and the SP mechanisms and that the oxygen uptake is independent of calmodulin.