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Regulation of the substance P‐induced contraction via the release of acetylcholine and γ‐aminobutyric acid in the guinea‐pig urinary bladder
Author(s) -
Shirakawa Junji,
Nakanishi Tateo,
Taniyama Kohtaro,
Kamidono Sadao,
Tanaka Chikako
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12615.x
Subject(s) - substance p , acetylcholine , tetrodotoxin , chemistry , endocrinology , medicine , contraction (grammar) , atropine , bicuculline , cholinergic , muscle contraction , muscarinic acetylcholine receptor , antagonist , biology , receptor , biochemistry , neuropeptide
1 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 (EC 50 =1.2 × 10 −9 m ). This contraction was not altered by tetrodotoxin, but with a dose of 10 −9 m and less, there was a complete inhibition by 10 −6 m atropine. Contractions initiated by 3 × 10 −9 m SP or more were partly inhibited by atropine. The EC 50 value of substance P in the presence of atropine was 7.0 × 10 −9 m . 2 Substance P induced a Ca 2+ ‐dependent and tetrodotoxin‐resistant release of [ 3 H]‐acetylcholine (ACh) from strips of urinary bladder preloaded with [ 3 H]‐choline (EC 50 = 4.9 × 10 −10 m ), and this release was antagonized by [D‐Pro 2 ,D‐Trp 7 ′ 9 ]substance P. 3 Bicuculline increased the substance P‐induced contraction and the release of [ 3 H]‐ACh from the strips. 4 Substance P induced a Ca 2+ ‐dependent and tetrodotoxin‐sensitive release of [ 3 H]‐γ‐aminobutyric acid (GABA) from strips preloaded with [ 3 H]‐GABA (EC 50 = 2.6 × 10 −9 m ), and this release was antagonized by [D‐Pro 2 ,D‐Trp 7 ′ 9 ]substance P. 5 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.