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Biomedical subjects

G Gacel

Publications and source records attributed to G Gacel.

At least 37 records · Page 2Linked to original sources
PubMed1984

Different effects of mu and delta opiate agonists on respiration.

The involvement of different opiate receptor subtypes in opiate-induced respiratory depression was studied in the unanaesthetized rat. Synthetic opioid agonists, specific for mu or delta receptors, were administered intraperitoneally in freely moving rats while respiratory parameters were recorded by means of the whole body plethysmographic method. TRIMU-4 (Tyr-D-Ala-Gly-NH-CH(CH3)-CH2-CH(CH3)2), a specific agonist of the mu receptor, reduced the tidal volume and did not change the respiratory frequency. DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr), a relatively specific agonist of the delta receptor subtype, reduced respiratory frequency and was significantly less effective on tidal volume than was TRIMU-4. It is concluded that the respiratory depression occurring after the administration of opiates in clinical practice is a dual complementary effect involving mu and delta receptors.

Animals↗
PubMed1984

Pharmacological identification of delta and mu opiate receptors on bulbar respiratory neurons.

The opiate receptors of central neurons related to the generation of the respiratory rhythm were identified using microiontophoresis of the synthetic opioid peptides DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr) and TRIMU-4 (Tyr-D-Ala-Gly-NH-CH (CH3)-CH2-CH(CH3)2), exhibiting a high selectivity for delta and mu receptors respectively. Both agonists induced depressions of spontaneous and L-glutamate-induced discharges; the effects were antagonized by naloxone and not mimicked by a related almost inactive peptide DSLLET (Tyr-D-Ser-Gly-Leu-Leu-Thr). The effect of DSLET had a faster time course than that of TRIMU-4 and persisted after prolonged applications of TRIMU-4. It is concluded that delta and mu receptors subtypes are distinct and are both present on central respiratory-related neurons.

Animals↗
PubMed1983

Deltakephalin, Tyr-D-Thr-Gly-Phe-Leu-Thr: a new highly potent and fully specific agonist for opiate delta-receptors.

Deltakephalin, Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) was rationally designed as pure delta-probe from proposed models of mu and delta opiate receptors. On peripheral organs, deltakephalin displays a 3000 times higher inhibitory potency on the electrically stimulated mouse vas deferens (IC50 = 0.15 nM) as on the guinea pig ileum (IC50 = 460 nM). As expected [3H]deltakephalin interacts at 35 degrees C in rat brain tissue to a single class of binding sites (delta) (Bmax = 0.115 pmole/mg protein) with a high affinity: KD = 1.35 nM from equilibrium measurements and KD = 0.43 nM from kinetic determinations. Deltakephalin occurs as the most specific ligand for delta-binding sites as shown by the following discrimination ratios KI(mu)/KI(delta): 0.31 for D-Ala2-D-Leu5-enkephalin; 0.15 for D-Ser2-Thr6-Leu-enkephalin and 0.05 for deltakephalin.

Animals↗
PubMed1983

Pain control by endogenous enkephalins is mediated by mu opioid receptors.

The analgesic effects of bestatin and thiorphan, two enzymatic inhibitors protecting endogenous enkephalins from their degradation, and those of DAGO and deltakephalin, respectively mu and delta opioid peptides, are assessed on the electrical stimulation test of the mouse tail. The relative analgesic potency of DAGO and deltakephalin is in good agreement with their relative potency on mu pharmacological assays: inhibition of electrically-induced contractions of guinea-pig ileum, displacement of 3H DAGO on rat brain. Finally, the analgesic effects of DAGO, deltakephalin and bestatin + thiorphan, are antagonized by the mu antagonist naloxone with similar pA2, and they are not modified by the delta antagonist ICI 154, 129. We conclude that only mu and not delta receptors are involved in the analgesic effects of enkephalins.

Amino Acids, Sulfur↗
PubMed1982

Enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity: selective radioassay, properties, and regional distribution in human brain.

The compound [3H]Tyr1,D-Ala2,Leu-OH5]enkephalin has been synthesised as a potentially selective substrate for enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity in brain. Incubations in the presence of homogenates and particulate fractions from rodent and human brain result in the formation of [3H]Tyr-D-Ala-Gly, which can be conveniently isolated by polystyrene bead column chromatography. The enzyme activity responsible for the hydrolysis of the Gly3-Phe4 amide bond of this substrate displays close resemblance to that hydrolysing the natural enkephalins at the same level. In addition, enkephalinase activity characterised in postmortem human brain is closely similar to that in rodent brain, with regard to optimal pH and apparent affinities of various substrates and inhibitors, including the potent compound thiorphan. Enkephalinase activity is distributed in a highly heterogeneous fashion among regions of human brain, the highest levels being found in globus pallidus and pars reticulata of the substantia nigra. This distribution is poorly correlated with that of opiate receptor binding sites but displays some resemblance to that of reported Met5-enkephalin levels.

Aged↗
PubMed1981

Evidence of the preferential involvement of mu receptors in analgesia using enkephalins highly selective for peripheral mu or delta receptors.

In order to study the preferential involvement of mu or delta receptors in the analgesic effects of enkephalins, several peptides which selectively interact with these two kinds of receptors in peripheral organs were synthesized. The inhibitory potency on the electrically stimulated mouse vas deferens (delta receptors) of the short peptide Tyr-D-Ala-Gly-NH-CH(CH3)CH2CH(CH3)2 (6) is 2100 times lower (IC50 = 1220 nM) than that of the longer and more hydrophilic peptide Tyr-D-Ser-Gly-Phe-Leu-Thr (10) (IC50 = 0.58 nM). In contrast, the IC50 values of all the synthesized compounds on the guinea pig ileum assay (mu receptors) are in the same range (100-360 nM). Likewise, their analgesic activities in mice, measured on the hot-plate test after intracerebroventricular injection, are similar. Therefore, the dissociation between antinociceptive properties in mice and potencies on the mouse vas deferens unambiguously reflects a preferential implication of mu receptors in analgesia. The possible involvement of brain delta receptors in behavioral effects is discussed.

Analgesia↗
PubMedDate not supplied

Synthesis and biological activity of Boc [Nle28, Nle31]CCK27-33, a highly potent CCK8 analogue.

A new CCK8 related peptide, Boc[Nle28,Nle31]CCK27-33 (Boc[diNle]CCK7) was synthesized and tested for cholecystokinic activity, at both the peripheral and the central level. This analogue, protected against both chemical oxidation and enzymatic degradation by aminopeptidases, was shown to be equipotent to CCK8 in releasing amylase from rat pancreas fragments. In addition, the EC50 values of Boc[diNle]CCK7 in the guinea pig gallbladder and ileum contraction assays (3.2 nM and 3.0 nM respectively) were similar to those of CCK8 (6.0 nM and 2.0 nM). Moreover both Boc[diNle]CCK7 and CCK8 elicited similar effects on the open field test over the same concentrations range. These results demonstrate the ability of Boc[diNle]CCK7 to be a suitable tool for investigating the physiological role of native CCK8.

Amylases↗