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R A Lefebvre

Publications and source records attributed to R A Lefebvre.

134 records · Page 8Linked to original sources
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Relaxant effect of rat PHI, PHI-Gly and PHV(1-42) in the rat gastric fundus.

It was previously shown that porcine PHI is 30 times less potent than VIP in relaxing the rat gastric fundus; the relaxant potency of rat PHI and its 2 C-terminally extended forms PHI-Gly and PHV(1-42) in the rat gastric fundus was compared here with that of VIP, porcine PHI and PHM. The rank order of potency in relaxing the precontracted fundus tissues was VIP greater than rat PHI greater than PHM greater than PHV greater than PHI-Gly greater than porcine PHI, rat PHI being only 2 times less potent than VIP. In the presence of antioxidants, the potency and efficacy of porcine PHI increased, but the peptide was still the least potent of the series tested. The results illustrate the importance of using species-related peptides and are compatible with a cotransmitter role of rat PHI in nonadrenergic noncholinergic neurotransmission of the rat gastric fundus.

Animals↗
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Influence of aging on gastric emptying of liquids, small intestine transit, and fecal output in rats.

The gastric emptying of a liquid meal, the small bowel transit, and the number of pellets and fecal output produced during a 24-h period, were studied in young (three months), adult (12 months) and old (24 months) male Wistar rats. The gastric emptying after 20 min of an intragastrically administered liquid meal containing phenol red and methylcellulose was significantly decreased in old rats. The small bowel transit after 15 and 30 min of the front of a charcoal and Arabic gum containing intragastrically administered meal was similar in the three age groups. The number of pellets and the mass of the feces produced during a 24-h period were significantly decreased with age, while the food intake was similar. The water content of the pellets was similar in the three age groups. These results show decreased gastric emptying of liquids and decreased stool mass in old rats, corresponding with the previously reported age-related changes in colonic smooth muscle contractility. Small intestinal transit was well maintained with age.

Aging↗
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Is peptide histidine isoleucine an inhibitory nonadrenergic noncholinergic neurotransmitter in the rat gastric fundus?

In the rat gastric fundus, vasoactive intestinal polypeptide (VIP) contributes to the nonadrenergic noncholinergic (NANC) inhibitory neurotransmission and coexists with its related peptide, peptide histidine isoleucine (PHI). As the two neuropeptides are co-released and have similar actions in different biological systems, the effect of PHI in the rat gastric fundus was studied in order to investigate whether it might be a co-transmitter of VIP in the inhibitory NANC neurotransmission in this tissue. Auxotonic responses were measured in longitudinal muscle strips from the gastric fundus of reserpinized rats (5 mg/kg i.p., 24 hr before sacrifice), suspended between parallel platinum electrodes in Krebs solution containing atropine (1 microM) and 5-hydroxytryptamine (3 microM). PHI induced concentration-dependent relaxations (10 nM-1 microM), qualitatively similar to those induced by electrical field stimulation (1 msec, supramaximal voltage, 0.25-16 Hz) and by VIP (0.3-100 nM), although PHI was about 30 times less potent than VIP. The submaximal relaxation induced by PHI (100 nM) was not influenced by tetrodotoxin (1 microM), hexamethonium (500 microM) and propranolol (10 microM) plus phentolamine (3 microM). Incubation during 60 min with a specific PHI-antiserum completely prevented the relaxation induced by PHI (100 nM) and reduced by 26% that induced by electrical field stimulation at 1 Hz; the procedure had no influence on the relaxation induced by VIP (3 nM) or isopropylnoradrenaline (10 nM). Incubation during 60 min with a specific VIP-antiserum completely prevented the relaxation induced by VIP (3 nM) and halved the relaxatory response to electrical field stimulation at 1 Hz, while it had no influence on the relaxation induced by PHI (100 nM) or isopropylnoradrenaline (10 nM). Control serum had no influence on any of the relaxant stimuli. In conclusion, PHI mimics the electrically induced NANC relaxation in the rat gastric fundus; its action is located at muscle level and does not involve alpha-, beta- or nicotinic receptors. The results obtained in the presence of the antisera provide further confirmation that VIP contributes to the NANC inhibitory neurotransmission of the rat gastric fundus and leave open the possibility that PHI is involved as co-transmitter.

Animals↗
PubMedDate not supplied

Effect of adenosine triphosphate and related purines in the rat gastric fundus.

The effect of adenosine triphosphate (ATP) and its analogues was studied in longitudinal muscle strips of the rat gastric fundus in order to characterize the purinoceptors involved. At resting tension, 10(-4) M ATP usually induced a small initial relaxation followed by a contraction; when tone was raised by administration of carbachol (10(-7) M), ATP (10(-4) M) induced a larger relaxation followed by a smaller rebound contraction. Both the contraction at resting tension and the rebound contraction were antagonized by indomethacin. With raised tone, both ATP and 2-methylthioATP induced concentration-dependent relaxations, followed by small rebound contractions, but the slope of the concentration-response curve was very shallow. alpha, beta-MethyleneATP and adenosine induced only concentration-dependent relaxations and the maximal effect was much more pronounced than that of ATP and 2-methyl-thioATP. The rank order of potency of the purines producing relaxation was 2-methylthioATP greater than alpha, beta-methyleneATP greater than ATP greater than adenosine. The relaxant effect of ATP (10(-4) M) at raised tone was clearly antagonized by both reactive blue 2 (10(-4) M) and desensitization to alpha, beta-methyleneATP. It is concluded that the contractile effect of ATP in the rat gastric fundus is due to stimulation of prostaglandin biosynthesis, but identification of the purinoceptor subtype mediating relaxation is problematic and it may differ from the P2x- and P2y-receptors, which are clearly distinguishable in a number of other tissues.

Adenosine Triphosphate↗
PubMedDate not supplied

Nitric oxide-mediated contraction in enteric smooth muscle.

Nitric oxide (NO) seems to be involved as neurotransmitter in nonadrenergic noncholinergic (NANC) smooth muscle relaxation throughout the gastrointestinal tract. Contractile responses to NO in the gastrointestinal smooth muscle have also been reported. In the guinea-pig ileal longitudinal muscle-myenteric plexus preparation at basal tone, NO induces a moderate relaxation followed by an aftercontraction; the latter is blocked by tetrodotoxin. The aftercontraction is also reduced by atropine, the remaining part being inhibited by a substance P antagonist. This indicates the activation of cholinergic and, possibly, tachykininergic neurons; it is not clear whether this represents a rebound phenomenon to the relaxation or a direct action of NO, initially masked by the relaxation. Nitrergic "off"-contractions, in response to electrical stimulation of the inhibitory NANC nerves, were reported in the opossum esophageal body and in the cat distal colon. Primary contractions to NO have been reported in the rat ileum and in the longitudinal muscle of the opossum esophagus. In the rat preparation, the contraction to NO is observed at lower concentrations than the relaxant effect. While the contraction in the opossum seems to be related to guanylate cyclase activation, this is not the case in the rat ileum, as methylene blue did not influence the contractions and 8-bromo-cGMP only had a relaxant effect. No clear-cut rise in cGMP was observed during the NO-induced contraction. The NO-induced contraction was also not influenced by ryanodine but it was concentration-dependently reduced by nifedipine, suggesting that it is related to extracellular calcium influx through L-type calcium channels. Primary contractions due to NO were also observed in the rat whole ileum and in the rat caecal longitudinal muscle, while aftercontractions, due to NO, were also obtained in the rat descending, transverse and sigmoid colon, as well as in the cat ileal longitudinal muscle.

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