Somatostatin selectively inhibits excitatory contractile pathways of the feline lower esophageal sphincter.
Intrinsic reflexes of the feline lower esophageal sphincter (LES) have been shown to be mediated by specific arrangements of excitatory peptidergic interneurons. Inhibition of intrinsic reflexes may also be mediated by neuropeptides. The specific aims of this study were: (1) to examine the effect of somatostatin (SOM) and vasoactive intestinal peptide (VIP) on basal LES tone, and (2) to determine if these transmitters exert selective inhibitory effects on excitatory contractile pathways. Intraluminal pressures were recorded from the LES, esophagus and fundus by a fixed perfused catheter assembly in anesthetized cats. Peptides were administered via the left gastric artery. SOM had no effect on basal LES pressure with doses ranging from 10(-9) to 10(-5) g/kg. VIP induced a dose-dependent inhibition of basal LES pressure. The maximal effective dose of VIP, 10(-6) g/kg, completely inhibited basal LES pressure (34.7 +/- 6.8 to 1.0 +/- 0.6 mmHg, P less than 0.001). We have previously shown that bombesin (BN) but not substance P (SP) or bethanechol contracts the LES via tetrodotoxin-sensitive pathways. BN at the D50 (5.10(-8) g/kg) increased LES pressure by 32.1 +/- 3.6 mmHg. SOM (10(-5) g/kg) decreased this BN response to 19.2 +/- 5.0 mmHg, P less than 0.05. In contrast, while the D50 of SP (5.10(-8) g/kg) gave a similar increase in LES pressure, 28.8 +/- 5.1 mmHg, this effect was not altered by SOM (23.8 +/- 6.7 mmHg, P greater than 0.10). SOM also had no effect on bethanechol-induced LES contractions (P greater than 0.10). VIP (10(-6) g/kg) totally inhibited the LES response to the D50 of BN, SP, and bethanechol. A submaximal dose of VIP (10(-7) g/kg) partially inhibited the contractile response of all three.


CONCLUSIONS
(1) VIP, but not SOM, inhibits basal LES tone. (2) SOM selectively inhibits BN but not SP- or bethanechol-induced LES contraction. (3) VIP inhibits BN, SP and bethanechol-induced LES contractions. These studies suggest that somatostatin can selectively inhibit excitatory interneurons at the LES.
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
H P
HP
Parkman
J C
JC
Reynolds
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D001839:Bombesin / Q000037:antagonists & inhibitors; D002415:Cats; D004576:Electromyography; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000294:innervation; D005748:Gastric Fundus / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D008297:Male; D008365:Manometry; D009119:Muscle Contraction / Q000187:drug effects*; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*; D013373:Substance P / Q000037:antagonists & inhibitors; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology*
D001626:Bethanechol Compounds; D018723:Bethanechol; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D001839:Bombesin