Search PubMed⌕ Search

Biomedical subjects

R Quirion

Publications and source records attributed to R Quirion.

At least 397 records · Page 22Linked to original sources
PubMed1982

Visualization and solubilization of rat brain opiate receptors with a "kappa" ligand selectivity pattern.

1. Specific binding of [3H]ethylketocyclazocine (EkappaC), a prototype kappa-opiate agonist, to slide-mounted rat striatal sections is increased in the presence of 100 mM NaCl at 4 degrees C. 2. Under similar incubation conditions, binding of mu and delta prototype opiates is reduced to almost undetectable levels. 3. Correlation (P less than 0.01) of the ligand selectivity pattern of [3H]EKC displacement with the potencies of various opiate drugs in inhibiting the contractions of the rabbit vas deferens, a kappa-opiate receptor bioassay, suggests that the binding site under study represents the pharmacologically relevant kappa-opiate receptor. 4. Visualization of these kappa-opiate receptors with tritium-sensitive film reveals a striking, highly discrete brain distribution pattern (e.g., striatal patches, habenular stripe) which is similar to that of [3H]dihydromorphine and [3H]naloxone. 5. Soluble [3H]EKC binding sites obtained from rat membranes also possess a kappa-like ligand selectivity pattern, with bremazocine being a potent displacer while mu and delta ligands are almost inactive. 6. A possible explanation of these data is that the "kappa"-opiate binding site in rat brain is one transitional state of an opiate receptor capable of assuming distinct conformations with characteristic ligand selectivity patterns. Other possibilities such as pre and post-synaptic locations should also be considered.

Animals↗
PubMed1982

Chronic phencyclidine treatment decreases phencyclidine and dopamine receptors in rat brain.

Chronic phencyclidine treatment (10 mg/kg/day, SC for 14 days) significantly decreased the number of [3H]phencyclidine and [3H]spiperone binding sites in rat brain. [3H]Dihydromorphine binding was not affected by the same treatment. An acute treatment with phencyclidine (10 mg/kg, SC) did not modify any of the binding sites under study. These results suggest that a chronic phencyclidine treatment induces a down-regulation of phencyclidine and dopamine receptors without affecting opiate receptors. These reductions in the number of phencyclidine and dopamine binding sites might be related to the development of tolerance and/or dependence to phencyclidine.

Animals↗
PubMed1982

Correlation of regional brain metabolism with receptor localization during ketamine anesthesia: combined autoradiographic 2-[3H]deoxy-D-glucose receptor binding technique.

LKB film autoradiography of 2-]3H]deoxy-D-glucose uptake shows that ketamine, administered in anesthetic doses, alters the pattern of metabolic activity in rat hippocampus. The labeled metabolic marker can be washed out of the slide-mounted tissue sections by preincubation to permit in vitro autoradiography of drug and neurotransmitter receptors in the same animal. In this way, opiate and phencyclidine receptor distributions may be correlated with patterns of glucose utilization in adjacent sections. If the observed relative enhancement of 2-deoxy-D-glucose uptake in the stratum moleculare of hippocampus reflects elevated metabolism in nerve terminals there, then the binding of ketamine to phencyclidine receptors on neurons in distant afferent sites, such as entorhinal cortex, may initiate the physiologic and metabolic effects.

Animals↗
PubMed1981

The hypotensive effect of centrally administered neurotensin in rats.

We have evaluated the cardiovascular effects of intracerebroventricular (i.c.v.) injections of neurotensin (NT) in pentobarbital-anesthetized rats. In most animals, the i.c.v. injection of NT (5.4, 10.8 and 16.2 nmol/rat) induced a dose-dependent fall of the arterial blood pressure. This effect was usually rapid in onset (30-60 sec) and of short duration (approximately 1-4 min). It was not preceded nor accompanied by any significant alteration of the heart rate. In about 25% of the animals, the vasodepressor effect of i.c.v. injections of NT was long lasting (30-45 min). Conscious rats were much less sensitive than anesthetized animals. The hypotensive effects of intravenously (i.v.) administered NT was fully maintained in animals made tolerant to the hypotensive effect of centrally administered NT. Similarly, the animals made unresponsive to i.v. injections of NT either by repeated i.v. injections of NT (e.g. tachyphylaxis) or by a chronic treatment with compound 48/80, still responded normally to centrally administered NT. The results suggest the existence of at least two anatomically distinct sites of action through which NT can induce hypotension in rats. One appears to be located in the periphery and the other, in the central nervous system.

Animals↗
PubMed1981

Differential neurobehavioral effects of neurotensin and structural analogues.

Neurobehavioral effects of neurotensin and structural analogues in which tyrosine in position 11 was replaced by either its d-isomer [D-Tyr11]-NT, phenylalanine [Phe11]-NT or D-phenylalanine [D-Phe11]-NT were studied. Results demonstrate that whereas neurotensin and [Phe11]-NT significantly decreased motor activity in rats, [D-Tyr11]-NT and [D-Phe11]-NT produced a marked and significant increase in activity. Such dichotomous action between analogues was not found for the hypothermic and muscular relaxation effects of neurotensin.

Animals↗
PubMed1981

Synthesis of peptides by the solid-phase method. 6. Neurotensin, fragments, and analogues.

Neurotensin (NT) and 24 related compounds, including fragments or analogues modified at the C-terminal end of the parent molecule, have been prepared by the solid-phase method. After purification by cation-exchange chromatography, the compounds were characterized by thin-layer chromatography, amino acid analysis, elemental analysis, and high-pressure liquid chromatography. The stimulating effects of the peptides were evaluated in rat stomach strips, in isolated spontaneously beating atria of guinea pigs, and in the coronaries of perfused rat hearts. The differences between the biological activities of these compounds are discussed.

Animals↗
PubMed1981

Phencyclidine (angel dust)/sigma "opiate" receptor: visualization by tritium-sensitive film.

[3H]Phencyclidine ([3H]PCP) binds specifically to an apparently single class of binding sites on slide-mounted sections of rat olfactory bulb (Kd = 46 nM; Bmax = 10.5 fmol per slice). Bound [3H]PCP can be displaced by nonradioactive PCP and a series of its analogs with relative potencies that correlate closely (P less than 0.001) with values determined in a rat discrimination test that utilized PCP as a cue. Although morphine, naloxone, and opiate peptides do not displace bound [3H]PCP, psychotomimetic benzomorphans, classed as "sigma opiates," are quite potent displacers in vitro and have PCP-like behavioral properties in vivo. These results suggest that phencyclidine and the sigma opiates act at the same sites. [3H]PCP binding sites were visualized by using tritium-sensitive LKB film analyzed by computerized densitometry and color coding. The [3H]PCP binds most densely to cortical areas, diffusely in neocortex, and somewhat heterogeneously in the laminae of the hippocampal formation and dentate gyrus. Most of the brainstem and spinal cord show low specific [3H]PCP binding, with gray matter generally showing more binding than white.

Animals↗
PubMed1980

Pharmacological studies of neurotensin, several fragments and analogous in the isolated perfused rat heart.

Neurotensin (NT) induced a dose-dependent increase of the coronary perfusion pressure (CPP) in the isolated perfused rat heart. This effect was not modified by pretreating the organ with methysergide (8.5 x 10(-6) M), atropine (3.4 x 10(-6) M), a mixture of phentolamine (3.1 x 10(-6) M) and practolol (1.5 x 10(-5) M), 8-leucine-angiomine (2.9 x 10(-5) M) thus suggesting the existence of specific NT receptors in the coronary vessels of rat. The structure-activity studies performed using several NT fragments and analogues in the isolated perfused rat heart led us to the following conclusions: (1) the minimum structure required for the full expression of the biological activity of NT is H-Arg9-Pro10-Tyr11-Ile12-Leu13-OH; (2) the amino acid Tyr in position 11 appears to play a key role in the process of NT receptor activation. The replacement of Tyr11 with Tyr(Me) gave a compound which inhibits selectively the increase in coronary perfusion pressure induced by NT, but still exhibits some NT-like activity, specially when used in concentrations higher than 10(-6) M. [Tyr(Me)11]NT did not antagonize the stimulant effects of NT in rat stomach strips and guinea pig atria, thus suggesting that the receptors mediating the constrictor effect of NT in coronary vessels of the rat are pharmacologically different from those subserving the stimulant effect of NT in rat stomach strip and guinea pig atria.

Animals↗
PubMed1980

Pharmacological characterization of neurotensin receptors in the rat isolated portal vein using analogues and fragments of neurotensin.

The contractile effects of the tridecapeptide neurotensin (NT) and several NT fragments and analogues were evaluated and compared in the rat isolated portal vein. The removal of the sequence pGlu1-Leu2-Tyr3-Glu4-Asn5-Lys6-Pro7 produced practically no change in the myotropic activity of NT while the deletion of Leu13 or the last 3 C-terminal amino acids (e.g. Tyr11, Ile12 and Leu13) gave compounds with very low agonist activity (NT(1-12)) or devoid completely of affinity and intrinsic activity (NT(1-10)). Replacing Tyr11 with Ala, Leu, D-Tyr or D-Phe markedly decreased the stimulant effect of NT but did not confer to the molecule antagonistic properties. On the other hand, the substitution of Try11 with D-Trp or Tyr(Me) gave NT analogues which behave as specific and competitive antagonist of the contractile effect of NT in the portal vein. pA2 values of [D-Trp11]-NT and [Tyr(Me)11]-NT measured in the venous preparation were similar to those found in the coronary vasculature of the rat. Taken all together, these results suggest that: (1) the minimum structure required for the full expression of the myotropic activity of NT in the rat portal vein is -Arg9-Pro10-Tyr11-Ile12-Leu13-OH; (2) Tyr11 appears to be closely involved in the process of NT receptor activation since its replacement with D-Trp or Tyr(Me) produced specific and competitive antagonist of NT; (3) the receptors mediating the contractile effect of NT in the rat portal vein appear to be pharmacologically similar to those found in the coronary vessels of the rat. The possibility for the existence of different types of NT receptor in other tissues is discussed.

Animals↗