Blockade of substance P receptors inhibits non-nicotinic, non-adrenergic colonic contractions induced by stimulation of the lumbar sympathetic nerves to the feline large intestine.
Experiments were performed on chloralosed cats, pretreated with guanethidine and hexamethonium and with ligated adrenals. The motility of an arterially isolated colonic segment was monitored by a volumetric method. Colonic contractions were induced either by electric stimulation of the centrally cut lumbar splanchnic nerves, or by close i.a. injections of acetylcholine (ACh). Close i.a. injections of substance P (SP) were performed in order to test the degree of SP-receptor blockade. Blockade of colonic SP-receptors, either by close i.a. administration of large amounts of SP itself or by Spantide, a competitive SP-receptor antagonist, markedly reduced or abolished the neurally induced colonic contractions, while responses to ACh were unchanged. These results indicate a role for SP, or a closely related peptide, as an intermediate neurotransmitter in the neurally induced colonic responses. Thus, the present study gives support to the hypothesis that non-nicotinic, non-adrenergic colonic contractions, in response to electric stimulation of sympathetic nerves, are due to an antidromic activation of sensory neurons with peripheral excitatory collaterals which release SP, in turn activating the colonic smooth muscle, mainly via a muscarinic mechanism.
L
L
Fändriks
C
C
Jönson
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D
Delbro
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002415:Cats; D003106:Colon / Q000294:innervation*; D004558:Electric Stimulation; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006145:Guanethidine / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007420:Intestine, Large / Q000294:innervation*; D008297:Male; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D013618:Tachyphylaxis
D006584:Hexamethonium Compounds; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; D018738:Hexamethonium; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-; D006493:Heparin; D000109:Acetylcholine; D006854:Hydrocortisone; D006145:Guanethidine