Serotonin depletion potentiates gastric secretory and motor responses to vagal but not peripheral gastric stimulants.
Vagal stimulation is known to release gastrointestinal serotonin. The effect of depletion of serotonin stores on vagally stimulated gastric acid secretion and motility was studied in rats. Pretreatment of rats with parachlorophenylalanine (p-CPA) did not alter basal gastric acid and serotonin secretion but produced a 57% reduction in the intraluminal gastric release of serotonin and a 43 to 100% potentiation of the gastric acid secretory response elicited by intracisternal injection of the stable thyrotropin-releasing hormone analog, RX 77368, in conscious pylorus-ligated rats or urethane-anesthetized rats with an acute gastric fistula. Dose-response studies revealed that the gastric acid secretion induced by submaximal but not high doses of RX 77368 was elevated significantly by p-CPA pretreatment. p-CPA also enhanced the gastric acid output produced by submaximal, but not high doses of the vagal stimulant baclofen, [beta-(p-chlorophenyl)-gamma-aminobutyric acid]. In contrast, p-CPA pretreatment had no effect on gastric acid secretion stimulated by bethanechol, histamine or pentagastrin. Selective depletion of central serotonin stores by pretreatment with the neurotoxin 5,7-dihydroxytryptamine given alone, or combined with parachloroamphetamine did not alter RX 77368-stimulated gastric acid secretion. In addition, gastric contractility stimulated by intracisternal injection of RX 77368 was significantly enhanced by p-CPA but not by 5,7-dihydroxytryptamine pretreatment, whereas the contractile response to carbachol was not altered by p-CPA pretreatment. These results suggest that depletion of peripheral but not central serotonergic stores potentiate gastric acid secretion and contractility induced by vagally, but not peripherally acting gastric stimulants. Thus, peripheral serotonin may exert an inhibitory tone on vagally stimulated gastric acid secretion and motility in the rat.
Stephens
R L
RL
Center for Ulcer Research and Education, Veterans' Administration Medical Center, Los Angeles, California.
Garrick
T
T
Weiner
H
H
Taché
Y
Y
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology / Q000031:analogs & derivatives; D014630:Vagus Nerve / Q000502:physiology*
D001626:Bethanechol Compounds; D018723:Bethanechol; D012701:Serotonin; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D001418:Baclofen; D010134:Fenclonine; D011761:Pyrrolidonecarboxylic Acid