Regulation of the substance P‐induced contraction via the release of acetylcholine and γ‐aminobutyric acid in the guinea‐pig urinary bladder

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Abstract
The action of substance P (SP) on the release of γ‐aminobutyric acid (GABA) and acetylcholine (ACh) and on contraction were studied in strips of the guinea‐pig urinary bladder. Substance P induced a dose‐dependent contraction of strips of guinea‐pig urinary bladder (EC50 =1.2 × 10−9m). This contraction was not altered by tetrodotoxin, but with a dose of 10−9m and less, there was a complete inhibition by 10−6m atropine. Contractions initiated by 3 × 10−9m SP or more were partly inhibited by atropine. The EC50 value of substance P in the presence of atropine was 7.0 × 10−9m. Substance P induced a Ca2+‐dependent and tetrodotoxin‐resistant release of [3H]‐acetylcholine (ACh) from strips of urinary bladder preloaded with [3H]‐choline (EC50 = 4.9 × 10−10m), and this release was antagonized by [D‐Pro2,D‐Trp7′9]substance P. Bicuculline increased the substance P‐induced contraction and the release of [3H]‐ACh from the strips. Substance P induced a Ca2+‐dependent and tetrodotoxin‐sensitive release of [3H]‐γ‐aminobutyric acid (GABA) from strips preloaded with [3H]‐GABA (EC50 = 2.6 × 10−9m), and this release was antagonized by [D‐Pro2,D‐Trp7′9]substance P. Therefore, substance P appears to exert excitatory effects on the contractility of urinary bladder predominantly by stimulating its own receptor located on the cholinergic nerve terminals. GABA released by substance P inhibits stimulation of the cholinergic neurone. However, the direct action of substance P on the cholinergic neurone is more potent that the indirect action via GABA release.
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