A. Balint et al., Functional and immunocytochemical evidence that galanin is a physiologicalregulator of human jejunal motility, J PHYSL-PAR, 95(1-6), 2001, pp. 129-135
The neuropeptide galanin has species-dependent effects on intestinal motili
ty. It has a contractile effect on rat jejunal muscle while it relaxes guin
ea-pig ileum by inhibiting cholinergic transmission. Its effect on human gu
t motility has been unknown. Extensive work led to the discovery of selecti
ve galanin analogues such as M 15 [galanin(1-12)-Pro-substance-P(5-11)], M3
5 [galanin(1-12)-Pro-bradykinin(2-9)-aniide] that competitively inhibit var
ious actions of galanin in the central nervous system. The present study wa
s designed to examine the effect of galanin, M 15 and M35 on longitudinal j
ejunal smooth muscle strips isolated from humans and rats, and to localize
galanin-immunoreactivity in human jejunum. Galanin and ACh were equally eff
ective in stimulating contractions of the isolated jejunal muscle: sigmoid
curve fitting showed that maximal contractile response to galanin and ACh w
ere 25.7 +/- 11.1 mN and 23.7 +/-9.7 in humans, while 8.0 +/-0.6 and 8.1 +/
-0.3 mN in rats. respectively. These effects of galanin were not inhibited
by either atropine (5x10(-6) M) or tetrodotoxin (3 x 10(-6) M). The potency
of galanin inducing the contractile actions were similar in humans and rat
s. Interestingly, neither M15 nor M35 (up to 10(-7) M) were able to inhibit
the responses of the smooth muscle to galanin. However, both putative gala
nin receptor antagonists showed agonist effects in our experimental models.
In accordance with the functional studies, both the longitudinal and the c
ircular muscle layers were abundant in nerve fibers and varicosities showin
g galanin immunoreactivity. Our data suggest that galanin is a potent physi
ological regulator of jejunal contractions in humans. Its action on the jej
unum, however, is mediated by galanin receptors that are different from tho
se located in the central nervous system. (C) 2001 Elsevier Science Ltd. Al
l rights reserved.