Effect of tachykinins on ascending and descending reflex pathway in rat small intestine.
OBJECTIVE
To examine the effect of tachykinins on the ascending reflex pathway in rat small intestine, we used different selective neurokinin (NK) receptor antagonists (RA): a) NK1-RA: GR-82334 and CP-96.345, b) NK2-RA: MEN-10.376 and L-659.877. The aim was further to investigate the effect of substance P (SP) on the ascending excitatory and descending inhibitory reflex pathway.


METHODS
The whole segments of rat ileum (10 cm in length) were studied in an organ bath. Ascending contraction of circle muscle was elicited by anal electrical stimulation (3 Hz, 1 ms, 20 V) and measured as change of intraluminal pressure by a perfused manometric system 2 cm and 4 cm orad of the stimulation site.


RESULTS
GR-82334 and CP-96.345 (NK1-RA) caused a significant dose-related inhibition of the oral contraction at a distance of 4 cm: GR-82334 [area: -10 % +/- 8 % (10 nmol/L); -29 % +/ -10 % (1000 nmol/L). P < 0.05, n = 10], CP-96.345 [area: -2 %+/- 6 %(0.1 nmol/L); -14 % +/- 10 % (10 nmol/L). P < 0.01, n = 8], whereas the contractile response at a distance of 2 cm was unaltered (n = 8). In contrast, MEN-10.376 and L-659.877 (NK2-RA) did not alter the amplitude or the area under the curve (n = 10). Neither the NK1- nor the NK2-receptor antagonists had a significant effect on the latency of the reflex response. SP showed a significant increase in the ascending contraction and the descending relaxation (n = 6, P < 0.01).


CONCLUSIONS
These results demonstrate that blockade of NK1-receptors decreases the oral reflex response. Latency of the reflex response remains unchanged, indicating that the effect is not due to an action on interneurons. NK2-receptors do not take part in the ascending reflex in rat small intestine. SP increases the descending relaxant reflex response and ascending contraction.
Hahn
Andreas
A
ll Medizinische Klinik und Poliklinik der Technischen Universitat M nchen, 81675 M nchen, Germany.
Storr
Martin
M
Allescher
Hans-Dieter
HD
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004525:Efferent Pathways / Q000187:drug effects; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010803:Physalaemin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D012018:Reflex / Q000187:drug effects*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology*
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C079014:GR 82334; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; D010803:Physalaemin; D013373:Substance P; D015288:Neurokinin A; C066892:CP 96345