Characterization of the effects of neurokinins on canine antral muscle.
The excitation of longitudinal antral muscle by substance P (SP) involves both a myogenic and a cholinergic effect. To examine if these responses are mediated by different neurokinin receptors, we studied the mechanical response and the release of [3H]acetylcholine from antral muscle strips in response to SP, substance P methylester (SPME), neurokinin A (NKA), neurokinin B (NKB), and several non-mammalian tachykinins. All peptides studied showed a dose-dependent inotropic and chronotropic effect on spontaneous phasic contractions. This ionotropic effect in longitudinal muscle was partially atropine sensitive for SPME, SP, and NKB but not for NKA, whereas neither atropine nor tetrodotoxin had an effect in circular muscle. In longitudinal muscle, all three neurokinins were equipotent. In longitudinal muscle treated with atropine and in circular muscle, the rank order of potency for the inotropic response was NKA greater than NKB greater than SP greater than SPME. For the chronotropic response the rank order was SPME, SP greater than NKA greater than NKB. NKA, NKB, and SP caused a dose-dependent, tetrodotoxin-sensitive increase in [3H]acetylcholine release from strips preincubated with [3H]choline. NKA was significantly more potent to release [3H]acetylcholine than either NKB or SP. The stimulated release was inhibited by [D-Ala2,D-Met5]methionine enkephalinamide and the SP antagonist, spantide. These results are consistent with the hypothesis that NKA is the natural ligand mediating the myogenic inotropic response in both muscle layers and the cholinergic response in longitudinal muscle.
Koelbel
C B
CB
Division of Gastroenterology, Harbor-UCLA Medical Center, Torrance 90509.
Mayer
E A
EA
van Deventer
G
G
Snape
W J
WJ
Patel
A
A
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004285:Dogs; D005260:Female; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015288:Neurokinin A / Q000494:pharmacology*; D015287:Neurokinin B / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D013373:Substance P / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D006584:Hexamethonium Compounds; D013373:Substance P; D018738:Hexamethonium; D013779:Tetrodotoxin; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D001285:Atropine; D015288:Neurokinin A; D015287:Neurokinin B; D000109:Acetylcholine