Putative mechanisms involved in excitatory and inhibitory effects of somatostatin on intestinal motility.
The mechanism of action of somatostatin on the motility of intestine was examined in the entire preparation and the longitudinal muscle attached with Auerbach's plexus (LA) preparation of guinea pig ileum, in relation to the cholinergic neuron and gamma-aminobutyric acid (GABA)ergic neuron. Somatostatin produced a transient potentiation of electrical stimulation-induced twitch contractions followed by an inhibition. The excitatory effect of somatostatin was associated with an increase in the release of [3H]acetylcholine (ACh) from the preparations preloaded with [3H]choline. Bicuculline, a GABAA antagonist, inhibited the somatostatin-induced excitatory effect. Somatostatin inhibited the electrical stimulation-induced twitch contraction and release of [3H]ACh, and the inhibition was greater in the entire preparation than in the LA. Phaclofen, a GABAB antagonist, prevented the inhibitory effects of somatostatin. Somatostatin induced a Ca2+ -dependent, tetrodotoxin-sensitive release of [3H]GABA from the preparations preloaded with [3H]GABA. Therefore somatostatin exerts excitatory and inhibitory effects on the cholinergic neuron due to the stimulation of the GABAergic neuron, and the motility of the intestine is regulated.
Takeda
T
T
Department of Pharmacology, Kobe University School of Medicine, Japan.
Taniyama
K
K
Baba
S
S
Tanaka
C
C
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D015016:Yohimbine; D009270:Naloxone; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D013806:Theophylline; D000109:Acetylcholine; D001640:Bicuculline