HCl-stimulated duodenal HCO3- secretion in conscious rat. Interactions among VIP, nicotinic receptor mechanisms, and prostaglandins.
Using an isolated loop of the proximal duodenum of conscious rats, the role of vasoactive intestinal peptide (VIP) in the duodenal HCO3- response to HCl was examined, especially interactions with participating cholinoceptor mechanisms and prostaglandins. A 5-min perfusion with 150 mmol/liter HCl increased luminal VIP during 3 hr, with a peak output during and immediately after the acid challenge. The HCl-stimulated output was unaffected by atropine and hexamethonium, but was augmented by indomethacin from 13.6 (9.5-17.8) to 39 (20-85) fmol/cm/min. The HCO3- secretion in response to graded doses of intravenous VIP (0.00625-6 nmol/kg/30 min) was dose-dependent to maximally 33.5 +/- 10.5 mumol/cm/hr. The HCO3- secretion during a single intravenous infusion of VIP (12 nmol/kg/hr), 13.9 +/- 4.2 mumol/cm/hr, was unchanged by atropine, reduced to 10.0 +/- 3.5 mumol/cm/hr by hexamethonium, and augmented to 18.9 +/- 4.7 mumol/cm/hr by indomethacin. Exogenous VIP did not change the basal luminal output of PGE2; neither did exogenous PGE2 nor indomethacin affect the basal luminal output of VIP. HCl-induced increases in luminal outputs of VIP, substance P, and neurokinin A (the two latter with unknown roles) were differentially affected by atropine, hexamethonium, and indomethacin, indicating that the acid challenge released the peptides through controlled mechanisms. In conclusion, in the duodenal HCO3- response to luminal HCl, VIP may have a stimulatory role, which partially depends on nicotinic, but not on muscarinic cholinoceptor mechanisms, and which is negatively modulated by prostaglandins.
Smedfors
B
B
Department of Internal Medicine, Karolinska Hospital, Stockholm, Sweden.
Theodorsson
E
E
Johansson
C
C
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism*; D018738:Hexamethonium / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000187:drug effects* / Q000494:pharmacology / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
D001639:Bicarbonates; D011978:Receptors, Nicotinic; D014660:Vasoactive Intestinal Peptide; D018738:Hexamethonium; D001285:Atropine; D015232:Dinoprostone; D006851:Hydrochloric Acid; D007213:Indomethacin