Cholinergic mechanisms involved in release and effect of prostaglandin E2 in HCl-stimulated duodenal HCO-3 secretion in the conscious rat.
Using a proximal duodenal loop in conscious rats, we investigated interactions between prostaglandin E2 and nicotinic and muscarinic receptor mechanisms previously found to be involved in the duodenal HCO3- response to HCl. In previous studies using the same model, a 5-min perfusion of the duodenal loop with 150 mmol l-1 HCl produced a marked and sustained HCO3- response. In the present study, the identical challenge produced a rapid 20-fold increase in the luminal output of prostaglandin E2 during acid exposure, followed by a sustained more than twofold elevation above the basal level during the 45 min monitored. The prostaglandin synthesis inhibitor indomethacin (4 mg kg-1 i.p.) suppressed the output of prostaglandin E2 during the HCl challenge from 131 +/- 84 to 15.4 +/- 10.0 pmol cm-1 h-1, and in the post-stimulatory period from 17.3 +/- 9.1 to 4.4 +/- 2.2 pmol cm-1 h-1. The nicotinic receptor antagonist hexamethonium (20 mg kg-1 i.v.) had no effect on the output of prostaglandin E2. The muscarinic receptor antagonist atropine (0.5 mg kg-1 s.c.) had no effect on the output of prostaglandin E2 during HCl challenge, but reduced the post-stimulatory output to 7.7 +/- 4.1 pmol cm-1 h-1. Perfusion of the duodenal loop with 0.1 mmol l-1 prostaglandin E2 produced a HCO3- response that was abolished by hexamethonium (20 mg kg-1 i.v.), but not affected by atropine (0.5 mg kg-1 s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)
Smedfors
B
B
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Aly
A
A
Hellström
P M
PM
Jaramillo
E
E
Johansson
C
C
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism* / Q000502:physiology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*
D001639:Bicarbonates; D006584:Hexamethonium Compounds; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D001285:Atropine; D015232:Dinoprostone; D006851:Hydrochloric Acid; D007213:Indomethacin