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

• Published in: British journal of pharmacology Vol. 98; no. 2; pp. 437 - 444
• Main Authors: Shirakawa, Junji, Nakanishi, Tateo, Taniyama, Kohtaro, Kamidono, Sadao, Tanaka, Chikako
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-1989; Nature Publishing
• Subjects: acetylcholine; Acetylcholine - metabolism; Animals; Atropine - pharmacology; Bicuculline - pharmacology; Biological and medical sciences; Calcium - physiology; Female; Fundamental and applied biological sciences. Psychology; gamma -aminobutyric acid; gamma-Aminobutyric Acid - metabolism; Guinea Pigs; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; In Vitro Techniques; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Muscle, Smooth - physiology; Parasympathetic Nervous System - drug effects; Parasympathetic Nervous System - physiology; Substance P - pharmacology; Tetrodotoxin - pharmacology; urinary bladder; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Vertebrates: endocrinology; Substance P; Rodentia; Muscle contraction; Neuropeptide; Vertebrata; Regulation(control); Mammalia; Guinea pig; Urinary system; Urinary bladder; GABA; Neurotransmitter; Acetylcholine; Release
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1989.tb12615.x

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 (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.
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 × 10−10m), 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]‐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.
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.