The site of action of capsaicin on the guinea-pig isolated ileum

Summary

The site and mode of action of capsaicin were analysed on the guinea-pig isolated ileum.

• 1. Capsaicin produced longitudinal contraction (EC₅₀ 4.2×10⁻⁸ g/ml) followed by a specific, rapid and irreversible tachyphylaxis (IC₅₀ 2.8×10⁻⁷ g/ml).

• 2. Capsaicin was ineffective in the presence of tetrodotoxin (2×10⁻⁷ g/ml) or on ilea kept for 24–48 h at 4°C, without an oxygen supply.

• 3. On ileal segments, the perivascular mesenteric nerves of which were transsected 5–8 days before the experiment, practically no response to capsaicin was obtained. Chronic abdominal bilateral vagotomy was without any effect.

• 4. Hyoscine (1×10⁻⁸–1×10⁻⁶ g/ml) or morphine (2×10⁻⁶ g/ml) strongly inhibited contractions produced by capsaicin. Neither mecamylamine (1×10⁻⁵ g/ml), nor nicotine (5×10⁻⁵ g/ml) and dimethylphenylpiperazinium (5×10⁻⁶ g/ml) caused any change, while an increased response to capsaicin was obtained in the presence of hexamethonium (1×10⁻⁴ g/ml).

• 5. Unaltered contractions were produced by capsaicin on ileal segments made tachyphylactic to 5-HT, bradykinin or substance P. Histamine antagonists at H₁ and H₂ receptors (chloropyramine, burimamide), the prostaglandin synthesis inhibitor indomethacin, pretreatment with the adrenergic neuron blocking agent guanethidine, as well as in vivo reserpine pretreatment were also ineffective in this respect.

• 6. It is concluded that in the guinea-pig ileum capsaicin causes predominantly cholinergic contraction by stimulating terminals of extrinsic, non-parasympathetic nerves.