Inhibitory effects of procaine on the contractile responses of the guinea-pig taenia caecum to acetylcholine, substance P and potassium chloride.

The effect of procaine on the contractile responses to acetylcholine, substance P and KCl was investigated using the isolated guinea-pig taenia caecum. In normal Tyrode solution (37 degrees C), procaine (10-100 mumol/l) caused a parallel shift to the right of only the dose-response curve of acetylcholine (pA2 value, 5.11). The pA2 value of procaine against acetylcholine was not significantly affected by increasing the Ca concentration in the bathing solution from 0.9 to 7.2 mmol/l. On the other hand, a high concentration of procaine (10 mmol/l) caused a transient contraction of the taenia caecum, but completely suppressed contractions to all concentrations of the agonists. In K-depolarized preparations, procaine (1-10 mmol/l) shifted the dose-response curve for the CaCl2-induced contraction to the right. Substance P (3 mumol/l)-induced contraction of the taenia caecum incubated with Ca-free EGTA (0.1 mmol/l) solution (20 degrees C) was markedly reduced by procaine (10 mmol/l). Using the single sucrose-gap technique, it was found that procaine (10 mmol/l) produced a membrane depolarization and increases in both amplitude and frequency of spontaneous spike discharge. These potential changes were still observed even after the procaine-induced contraction had disappeared. The spike discharges and contraction caused by procaine were abolished in the presence of a Ca-entry blocker, verapamil (10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)