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R A Lefebvre

Publications and source records attributed to R A Lefebvre.

At least 127 records · Page 7Linked to original sources
PubMed1987

Identification and characterization of peripheral neuronal dopamine receptors in the rat.

The effects of local administration of the dopamine receptor agonists apomorphine and pergolide were investigated in the isolated autoperfused hindquarters, renal and superior mesenteric vascular beds of the rat, in order to assess whether presynaptic dopamine receptors in these vascular regions could play a role in the hypotensive effect of these agents. In the three vascular beds, local infusion of apomorphine and pergolide did not influence perfusion pressure per se, but clearly reduced the pressure response to electrical stimulation of the sympathetic innervation. Increases in perfusion pressure induced by local administration of noradrenaline were not influenced by apomorphine and pergolide. The inhibitory effect of apomorphine and pergolide on stimulation-evoked pressure responses was completely antagonized by the dopamine receptor antagonist haloperidol. The alpha 2-adrenoceptor antagonist rauwolscine, which completely blocked the inhibitory effect of the alpha 2-adrenoceptor agonist UK-14,304-18 on neurogenic vasoconstriction, had no influence on the inhibitory effect of apomorphine and pergolide. Like haloperidol, the DA2-receptor antagonist domperidone antagonized the inhibition of neurogenic vasoconstriction by apomorphine in the three vascular beds; the DA1-receptor antagonist SCH 23390 had no influence. These results indicate that inhibitory DA2-receptors are present on the sympathetic innervation to the hindquarters, renal and superior mesenteric vascular beds of the rat.

Animals↗
PubMed1986

Emetic and antiemetic effects of opioids in the dog.

The emetic and antiemetic effects of opioid agonists were studied in awake dogs. The mu-agonists morphine, fentanyl and methadone, in sedative doses, prevented the emetic response to apomorphine and copper sulphate; only morphine induced emesis, at doses lower than those required to prevent emesis. The delta-agonist [D-Ala2,Met5]enkephalinamide (DALA) and [Leu5]enkephalin induced emesis in some of the dogs studied but had no antiemetic activity. The kappa-agonists bremazocine and ethylketocyclazocine (EKC) did not induce emesis but, at sedative doses, prevented the emetic response to apomorphine. The emetic effect of DALA was antagonized by naloxone in some dogs; the antiemetic effect of morphine, bremazocine and EKC was blocked by both naloxone and MR 2266. The non-opioid sedatives diazepam, phenobarbital and xylazine, administered in sedative doses, did not prevent apomorphine-induced emesis. Our results suggest that a delta-receptor is involved in the emetic effect and a mu- and/or or kappa-receptor in the antiemetic effect of opioids.

Animals↗
PubMed1986

Inhibition of noradrenergic neurotransmission by apomorphine and pergolide in the in situ autoperfused rat renal and superior mesenteric vascular beds.

In vitro studies have provided evidence that presynaptic dopamine receptors are present in the rat renal and superior mesenteric vascular beds. To confirm this in vivo, the effects of locally administered apomorphine and pergolide were studied in the in situ autoperfused renal and superior mesenteric vascular beds. Local infusion of apomorphine (1 microgram X kg-1 X min-1 for 5 min) or pergolide (1 microgram X kg-1 X min-1 for 5 min) into either the renal or the superior mesenteric artery had no effect on perfusion pressure per se. In the renal vascular bed, the pressure response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) was reduced to 49.8 +/- 4.8% by apomorphine and to 54.8 +/- 2.7% by pergolide; in the mesenteric vascular bed, apomorphine reduced the pressure response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) to 53.8 +/- 2.9, pergolide to 52.0 +/- 1.8%. Increases of perfusion pressure in the renal and in the mesenteric vascular bed induced by locally administered noradrenaline were not modified by apomorphine or pergolide. In both vascular beds, the inhibition of the stimulation-evoked pressure responses by apomorphine or pergolide was completely antagonized by local administration of the dopamine receptor antagonist haloperidol in a dose (1 microgram X kg-1) which did not influence the inhibitory effect of the alpha 2-adrenoceptor agonist UK-14,304; the alpha 2-adrenoceptor antagonist rauwolscine, in a dose (100 micrograms X kg-1) which completely antagonized the inhibitory effect of UK-14,304, did not antagonize the inhibitory effects of apomorphine and pergolide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Pharmacological characterization of neuronal dopamine receptors in the rat hindquarters, renal and superior mesenteric vascular beds.

The present study was designed to characterize the neuronal dopamine receptors involved in the inhibitory effect of apomorphine on neurogenic vasoconstriction in the isolated autoperfused hindquarters, renal and superior mesenteric vascular beds of the rat. In the three vascular beds, the inhibitory effect of apomorphine on neurogenic vasoconstriction was antagonized by the selective DA2-receptor antagonist domperidone, but not by the selective DA1-receptor antagonist SCH 23390. Local administration of these antagonists had no effect on the perfusion pressure per se or on the pressure response to electrical stimulation of the sympathetic innervation. These results show that the neuronal dopamine receptors present in the rat hindquarters, renal and superior mesenteric vascular beds can be classified as DA2-receptors.

Animals↗
PubMed1986

Neither morphine nor clonidine influence the non-adrenergic, non-cholinergic inhibitory response in the rat gastric fundus.

Morphine and clonidine are among the few agents reported to modulate non-adrenergic, non-cholinergic (NANC) responses in different tissues. They were therefore tested for their effect on the NANC inhibitory response in the rat gastric fundus. Neither morphine (10(-5) M), nor clonidine (10(-5) M in the presence of prazosin 10(-6) M to avoid its own relaxatory effect) modified the NANC response in the rat gastric fundus.

Animals↗
PubMed1986

In-vitro study of the enkephalinergic hypothesis for non-adrenergic, non-cholinergic innervation in the cat stomach.

It has been suggested that enkephalins are involved in the gastric relaxation induced by stimulation of the non-adrenergic, non-cholinergic vagal fibres in the cat stomach. Experiments were therefore performed on strips of cat stomach. With longitudinal and circular gastric fundus and corpus strips from reserpinized cats, non-adrenergic, non-cholinergic relaxatory responses could be elicited by transmural electrical stimulation in Tyrode solution containing atropine and 5-hydroxytryptamine. Morphine, leu-enkephalin and met-enkephalin did not influence the tone of the strips or the relaxation evoked by stimulation at 8 Hz, and neither did the opioid antagonist, naloxone. These results do not support the enkephalinergic hypothesis for the non-adrenergic, non-cholinergic vagal fibres in the cat stomach.

Animals↗
PubMed1986

Study on the possible neurotransmitter of the non-adrenergic non-cholinergic innervation of the rat gastric fundus.

The neurotransmitter of the non-adrenergic non-cholinergic inhibitory innervation of the stomach is still unknown. We studied the effect of a series of neurotransmitter candidates, ATP, [Leu]enkephalin and [Met]enkephalin, somatostatin, neurotensin and VIP, in the rat gastric fundus and compared these effects with the response to electrical stimulation of the non-adrenergic non-cholinergic inhibitory neurons. Rats of both sexes were treated with reserpine (5 mg . kg-1 intraperitoneally) 24 h before killing. Longitudinal muscle strips of the gastric fundus were prepared and mounted between parallel platinum electrodes in Krebs solution containing atropine 10(-6) M and serotonin 3.10(-6) M. A maximal relaxatory response was obtained on transmural stimulation of the strips at supramaximal voltage, 1 msec and 5 Hz. ATP (10(-6)-10(-3) M) elicited a biphasic response, a small relaxation followed by a contraction. The maximal relaxatory response induced by ATP was much lower than that induced by transmural stimulation during 45 sec (37.3% versus 166.2%, where 100% is the maximal contractile response to ATP, n = 17). Desensitization to ATP did not influence the relaxation induced by transmural stimulation. [Met]enkephalin, [Leu]enkephalin and naloxone did not change the tone of the strips or the amplitude of the electrically induced relaxation. Somatostatin had no influence while neurotensin induced a concentration-dependent contraction from 10(-9) M or 10(-8) M on. VIP (10(-10)-3.10(-8) M) induced a concentration-dependent relaxation. The maximal relaxation induced by VIP was 120.8% of that induced by transmural stimulation (n = 16). The relaxation induced by VIP 10(-8) M, left in contact with the tissue for 10 min, was comparable to that induced by transmural stimulation during 10 min, except for a lag time of more than 10 sec after the addition of VIP. The relaxation induced by VIP was not influenced by tetrodotoxin, phentolamine or propranolol. The peptidase trypsin (10(-6) M) antagonized the relaxation by exogenously added VIP but did not influence the electrically induced relaxation. The results obtained in this study show that, of the substances tested, only VIP mimics the relaxation induced by stimulation of the inhibitory non-adrenergic non-cholinergic neurons in the rat gastric fundus; VIP therefore seems a reasonable candidate as neurotransmitter of these neurons.

Adenosine Triphosphate↗
PubMed1985

Influence of peripheral and central administration of apomorphine and morphine on intragastric pressure in the dog.

Apomorphine was about 30 times more potent in inducing gastric relaxation when applied intracerebroventricularly (i.c.v.) than when injected intravenously (i.v.) in the conscious dog. In the anesthetized dog, the dose of apomorphine producing gastric relaxation via the vertebral artery was at least 10 times lower than that needed to produce gastric relaxation via the i.v. route. For morphine, similar doses had to be given i.c.v. and i.v. to obtain the same degree of gastric relaxation in the conscious dog; in the anesthetized dog, morphine was 3 times more potent via the vertebral artery than i.v. The results suggest that apomorphine-induced gastric relaxation in the dog is mediated via a central site located in the region supplied by the vertebral artery, but that the gastric relaxatory effect of morphine is mediated by both a peripheral and a central site of action.

Animals↗
PubMed1985

Inhibitory effects of apomorphine and pergolide on neurogenic vasoconstriction in the hindquarters of the rat.

The effects of locally administered apomorphine and pergolide were studied in the isolated autoperfused hindquarters of the rat, in an attempt to assess the possible role of presynaptic dopamine receptors at that level in the hypotensive effect of these dopamine agonists. Local infusion of apomorphine (1 micrograms . kg-1 . min-1 for 5 min) or pergolide (1 micrograms . kg-1 . min-1 for 5 min) [into the hindquarters] did not alter perfusion pressure per se, but reduced the pressor response to electrical stimulation of the lumbar sympathetic chains for the whole frequency range used during a cumulative frequency-response curve (0.25-16 Hz, 1 ms, supramaximal voltage). Apomorphine and pergolide reduced the pressor response elicited by 4 Hz electrical stimulation (applied until maximum response was reached) to 54.8 +/- 7.1% and 53.9 +/- 1.7% respectively, but they did not modify similar increases of perfusion pressure produced by locally administered noradrenaline. The inhibition by apomorphine and pergolide of the 4 Hz stimulation-evoked pressor response was completely antagonized by local administration of the dopamine antagonist haloperidol (1 microgram . kg-1), but was not influenced by the alpha 2-antagonist rauwolscine (100 micrograms . kg-1). This dose of rauwolscine antagonized the inhibitory effect of the alpha 2-agonist UK-14,304, which was not influenced by haloperidol. Local administration of rauwolscine increased the pressor response to stimulation at 4 Hz by 37.4-46.2%. In contrast, local administration of haloperidol did not influence the 4 Hz stimulation-evoked pressor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Pharmacological characterization of the postjunctional beta-adrenoceptors in the rat gastric fundus.

In order to characterize the postjunctional beta-adrenoceptors in the rat gastric fundus, we studied the influence of beta-agonists and beta-antagonists on methacholine-contracted fundus strips. The mixed beta-agonist isopropylnoradrenaline and the beta 2-selective agonist fenoterol had a concentration-dependent relaxing effect and at higher concentrations completely inhibited the methacholine-induced tone. The reputedly beta 1-selective agonist prenalterol only produced about 50% inhibition and another reputedly beta 1-selective agonist, tazolol, had almost no relaxing effect. The beta-antagonists propranolol (beta 1 + beta 2), practolol (beta 1), H35/25 (beta 2) and ICI 118,551 (beta 2) all shifted the concentration-response curves for isopropylnoradrenaline and fenoterol in a parallel way to the right, but the slope of the Schild plot was not significantly different from 1 only for the antagonism of isopropylnoradrenaline by H35/25. The relaxing effect of prenalterol was only clearly antagonized by ICI 118,551. The results suggest that postjunctional beta 1- and beta 2-adrenoceptors are present in the rat gastric fundus.

Adrenergic beta-Agonists↗
PubMed1984

Inhibitory effect of dopamine on canine gastric fundus.

The mechanism of the inhibitory effect of dopamine on canine stomach fundus was studied in longitudinal and circular muscle fundus strips, contracted by transmural electrical stimulation or by methacholine. Results obtained for longitudinal and circular strips were similar. Dopamine (1 X 10(-6)-1 X 10(-4) M) concentration-dependently inhibited frequency-response curves to electrical stimulation; these concentrations did not change the resting tone of the strips. Dopamine (1 X 10(-4) M), tested on contractions of similar amplitude induced in the same strips by electrical stimulation at 0.5 Hz and by methacholine, inhibited the electrically induced contractions but had little influence on the contractions induced by methacholine. The inhibition of the electrically induced contractions by dopamine 1 X 10(-4) M was not influenced by the presence of cocaine 3 X 10(-5) M or hydrocortisone 3 X 10(-5) M. The alpha 1- and alpha 2-adrenoceptor antagonist phentolamine and the alpha 2-adrenoceptor antagonist rauwolscine markedly antagonized the inhibitory effect of dopamine on the response to electrical stimulation at 0.5 Hz. The alpha 1-adrenoceptor antagonist prazosin and the dopamine receptor antagonists haloperidol and domperidone had no effect. The dopamine receptor antagonist metoclopramide decreased the inhibitory effect of dopamine but had a similar effect on the inhibition caused by noradrenaline. These results indicate that the inhibitory effect of dopamine in the dog gastric fundus is mainly mediated by an interaction with alpha 2-adrenoceptors on the intramural cholinergic neurons; this effect is largely direct since it was not influenced by cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1984

Pharmacological characterization of alpha adrenoceptors in the rat gastric fundus.

Alpha receptors on the intramural cholinergic neurons and on the smooth muscle cells are involved in the inhibitory effect of catecholamines on rat gastric fundus motility. The pharmacological characteristics of these alpha receptors were assessed using longitudinal muscle strips of the rat gastric fundus, contracted to a similar degree by electrical stimulation and by methacholine. All alpha agonists studied (norepinephrine, phenylephrine, methoxamine, clonidine, UK-14,304 and B-HT 920) concentration-dependently inhibited the stimulation-induced contractions. Norepinephrine, phenylephrine, methoxamine and clonidine also inhibited the methacholine-induced contractions, but for the same concentration of agonist, the inhibition was less pronounced than during electrical stimulation-induced contractions; UK-14,304 and B-HT 920 inhibited the methacholine-induced contractions only in a concentration of 10(-4) M. The effect of clonidine and UK-14,304 on electrical stimulation-induced contractions was antagonized competitively by the alpha antagonists rauwolscine and yohimbine (slope in the Schild plot not different from 1). The effect of norepinephrine and phenylephrine on methacholine-induced contractions was antagonized by the alpha antagonists prazosin, corynanthine and yohimbine; against phenylephrine, the antagonism was competitive (slope in the Schild plot not different from 1). It is concluded that the muscular alpha receptors in the rat gastric fundus are of the alpha-1-type. On the postganglionic cholinergic neurons, alpha-2-like receptors are present; it is not yet clear whether the pronounced effect of alpha-1 agonists on the cholinergic neuron activity is due to interaction with these receptors.

Adrenergic alpha-Agonists↗
PubMed1981

Gastric relaxation and vomiting by apomorphine, morphine and fentanyl in the conscious dog.

Apomorphine (0.03 mg . kg-1 s.c.) and morphine (0.5 mg . kg-1 s.c.) produced gastric relaxation and vomiting in the conscious dog. Domperidone (0.1-1 mg . kg-1 i.v.), haloperidol (0.1 mg . kg-1 i.v.) and pimozide (0.025 mg . kg-1 i.v.) selectively blocked the gastric relaxation as well as the vomiting caused by apomorphine. Naloxone (0.07 mg . kg-1 i.v.) selectively blocked the gastric relaxation and the vomiting caused by morphine; after naloxone, morphine produced a delayed gastric relaxation in 2 experiments out of 7. These results suggest that for gastric relaxation as well as for vomiting, apomorphine and morphine act on different receptors. Fentanyl elicited marked gastric relaxation, blocked by naloxone, but did not elicit vomiting. After fentanyl, morphine and apomorphine no longer produced gastric relaxation and vomiting. This observation shows that the known blocking effect of fentanyl at the vomiting center does not affect its gastric relaxing effect.

Animals↗