Tachykinins contract the circular muscle of the human esophageal body in vitro via NK2 receptors.
BACKGROUND
The action of tachykinins in the circular muscle of the human esophageal body is not known. The present study aimed to determine the response to tachykinins and the receptor type mediating this response.


METHODS
Specimen were obtained from organ donors or patients undergoing esophagectomy for cancer, and isometric tension in response to tachykinins was measured.


RESULTS
Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) evoked a concentration-dependent contraction with the following order of potency: NKA > NKB > SP. The neutral endopeptidase inhibitor, phosphoramidon, increased only the response to SP. [beta Ala8]NKA(4-10), a selective agonist of the NK2 receptor, produced a concentration-dependent contraction, whereas [Sar9,Met(O2)11]SP and [MePhe7]NKB, selective agonists of NK1 and NK3 receptors, respectively, had no effect. Contraction evoked by NKA was inhibited by the nonpeptide NK2 antagonist SR 48968 but not by the nonpeptide NK1 receptor antagonist CP-96,345, tetrodotoxin, or atropine. SR 48968 did not affect the response to carbachol.


CONCLUSIONS
Tachykinins contract the circular muscle of human esophageal body by activation of NK2 receptors without involvement of neural mechanisms. Response to SP is modulated by a phosphoramidon-sensitive enzymatic activity.
Huber
O
O
Department of Surgery, University of California, San Francisco.
Bertrand
C
C
Bunnett
N W
NW
Pellegrini
C A
CA
Nadel
J A
JA
Debas
H T
HT
Geppetti
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007537:Isometric Contraction; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D015260:Neprilysin / Q000037:antagonists & inhibitors; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018039:Receptors, Tachykinin / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001549:Benzamides; D001713:Biphenyl Compounds; D006020:Glycopeptides; D010880:Piperidines; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; D013779:Tetrodotoxin; C073839:SR 48968; D001285:Atropine; D015288:Neurokinin A; D015287:Neurokinin B; D002217:Carbachol; D015260:Neprilysin; C008890:phosphoramidon; C066892:CP 96345