Regulation of the substance P-induced contraction via the release of acetylcholine and gamma-aminobutyric acid in the guinea-pig urinary bladder.
1. The action of substance P (SP) on the release of gamma-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 x 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 x 10(-9) M) SP or more were partly inhibited by atropine. The EC50 value of substance P in the presence of atropine was 7.0 x 10(-9) M. 2. 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 x 10(-10) M), and this release was antagonized by [D-Pro2,D-Trp7,9] substance P. 3. Bicuculline increased the substance P-induced contraction and the release of [3H]-ACh from the strips. 4. Substance P induced a Ca2+-dependent and tetrodotoxin-sensitive release of [3H]-gamma-aminobutyric acid (GABA) from strips preloaded with [3H]-GABA (EC50 = 2.6 x 10(-9) M), and this release was antagonized by [D-Pro2,D-Trp7,9] 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.
Shirakawa
J
J
Department of Pharmacology, Kobe University, School of Medicine, Japan.
Nakanishi
T
T
Taniyama
K
K
Kamidono
S
S
Tanaka
C
C
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D013373:Substance P; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D001285:Atropine; D000109:Acetylcholine; D002118:Calcium; D001640:Bicuculline