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Bury RW, Mashford ML.
“A Pharmacological Investigation of Synthetic Substance P on the Isolated Guinea-Pig Ileum”.
Clin.Exp.Pharmacol.Physiol.. 1977;4(5):453-61.
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Abstract
The effect of substance P (SP) on guinea-pig ileum in-vitro was studied. Segments of distal ileum of guinea-pigs were set up in aerated : Tirade Solution at 320. Atropine (up to 5.8 EM, Bull) did not effect responses to SP. This was 100x the concentration required to abolish responses to ACh (11 nM, Koch-Light). Mepyramine (up to 10 pM, Bull) did not affect responses to SP, but ACh responses were reduced to 550f control levels and responses to histamine (26 nM, Bull) were abolished by 0.1 I1M mepyramine. Hexamethonium ( , 1.1 mM, Koch-Light) had a non-specific potentiating action on responses to SP and ACh; 0.11 mM blocked the action of nicotine (—.2-12 uM, Woods) but did not reduce responses to SP. Cyproheptadine (11 mcM, Merck-USA) reduced responses to SP by 48% which was 10x the concentration required to abolish responses to serotonin (1.0- 2.5 mcM, 5-HT, Koch-Light) and ACh. Morphine (5.3 nM-5.3mcM, Bull) reduced responses to 5-HT by 90% but did not effect those of SP or ACh. Phenoxybenzamine (1.2 mcM. SK+F) reduced responses to SP (35%), ACh (60%) and 5-HT (81%). Methysergide (8.5 mcM, Sandoz) potentiated responses to SP and ACh and partially reversed antagonism to 5-HT effected by a concentration of up to 0.85 mcM. Lysergide (95 and 240 nM LSD 25, Sandoz) potentiated responses to SP and ACh and reduced responses to 5-HT by 43%. BOL (up to 7.2 pM, Sandoz) progressively decreased responses to SP (58%), ACh (54%) and 5-HT (72%). 5-HT (5 pM) in the bathing fluid reversibly reduced responses to SP (53%) and ACh (62%). Indometha cin (up to 100 /mcM, Merck-USA) decreased responses to SP (59%) and ACh (50%). Tetrodotoxin (12.5 nM-1.25 mcM, Sankyo) did not effect responses to SP but 125 nM blocked the responses of nicotine. Pentobarbitone (16 mcM, May+Baker) equally depressed rest ponses to SP and ACh Phenytoin (1.5-150 mcM, Parke-Davis), chlordiazepaxide (0.12-120 mcM, Roche) and q-tetrahydrocannabinol (0.13-130 mcM) produced non-specific decreases in responses to SP and ACh. Fluphenazine (Squibb) was 20x more potent than pentobarbitone, but was still unspecific. Amitryptyline (0.13 M) strongly antagonized SP and bradykinin but more markedly ACh. Pimozide (8.7 nM-8.7 mcM, Ethnor) abolished by up to 70% the responses to SP and ACh. Strychnine (0.98-98 mcM, Koch-Light) reduced SP and ACh responses by a maximum of 70%. Leptazol (2.9 290 mcM, Knoll) did not significantly effect SP and ACh responses. Amantadine (up to 210 M, CIBA-Geigy) caused little antagonism to SP and bismuth subgallate (up to 970 mcM, Allen+Hanbury) had no effect on SP responses.
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