Substance P: a potent inhibitor of the canine small intestine in vivo.
Intra-arterially administered substance P inhibited neurally activated contractions of the circular muscle of canine small intestine in vivo (lowest effective dose approximately 10(-13) mol). Excitation of intestine required higher (10(-10) mol) doses. The inhibitory effect required functioning nerves, since tetrodotoxin treatment eliminated it. However, inhibition of neurogenic contraction by substance P was unaffected by nicotinic or opiate receptor antagonists or by catecholamine depletion but was reduced by a selective substance P antagonist. Since the inhibition by substance P was also greatly reduced by treatment with atropine or pirenzepine and acetylcholine given intra-arterially produced a similar inhibitory response, stimulation of release of acetylcholine to inhibitory muscarinic receptors on nerves appeared to be the mechanism of this action. Direct smooth muscle effects were ruled out; substance P did not inhibit contractions to intra-arterial acetylcholine or those following tetrodotoxin. In vitro in ileal strips, no inhibition by substance P of any contractile response was found. We propose that the local release of substance P into the myenteric plexus produces inhibition and suggest that this constitutes a physiological function of the neuropeptide. This action may be absent in vitro.
J E
JE
Fox
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EE
Daniel
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects*; D008297:Male; D009037:Motilin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010890:Pirenzepine; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001570:Benzodiazepinones; D006584:Hexamethonium Compounds; D009294:Narcotics; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D011957:Receptors, Opioid; D013373:Substance P; D009270:Naloxone; D010890:Pirenzepine; D013779:Tetrodotoxin; D009037:Motilin; D004744:Enkephalin, Methionine; D001285:Atropine; D012110:Reserpine; D000109:Acetylcholine; D009638:Norepinephrine