Influence of changed calcium and potassium concentration on the algesic effect of bradykinin and acetylcholine

Summary

• 1. In the isolated perfused rabbit ear bradykinin (B) and acetylcholine (ACh) stimulate paravascular pain receptors. Changed calcium (Ca²⁺) and potassium (K⁺) concentrations were used to investigate whether there were different “pharmacological” receptors for B and ACh.

• 2. Increased [K⁺] (26.8 mM) lowered the pain threshold for both B and ACh. Decreased [K⁺] (0.27 mM) did not alter the algesic effect of B or ACh.

• 3. Increased [Ca²⁺] (3.6 and 9.0 mM) strongly enhanced the algesic effect of ACh but reduced that of B. Decreased [Ca²⁺] (0.18 and 0.6 mM) also reduced the algesic effect of B but did not influence that of ACh. Single i.a. injections of CaCl₂ (1–5 mg) directly stimulated paravascular pain receptors.

• 4. Prostaglandin E₁ (PGE₁, 10 ng/ml) reversed the inhibitory influence of 9 mM [Ca²⁺] on the B effect and further enhanced the Ca²⁺-facilitated ACh effect.

• 5. Conclusion. ACh and B exert their algesic effect via different receptor sites. This was concluded from the use of changed [Ca²⁺] and [K⁺]. High [K⁺] increased the effect of B and ACh due to membrane depolarization. Low [Ca²⁺] diminished only the effect of B but not that of ACh. High [Ca²⁺] increased the algesic effect of ACh possibly due to an enhanced Ca²⁺ influx at the generator region thus contributing to excitation. This finding is substantiated by the fact that Ca²⁺ by itself in sufficiently high amounts can stimulate pain receptors. High [Ca²⁺] reduced the effect of B by interfering with the pain enhancing action of PGE released by B, the algesic effect of which being strongly dependent on the presence of PGE.

An interference of high [Ca²⁺] with the direct effect of B is rather unlikely since during inhibited PGE-release high [Ca²⁺] no longer reduces significantly the effect of B.