Biomedical subjects

J R Naranjo

Publications and source records attributed to J R Naranjo.

62 records · Page 4Linked to original sources

PubMed1983

Substance P-induced release of Met5-enkephalin from striatal and periaqueductal gray slices.

Substance P(SP), the heptapeptide SP and the stable analogue (p-Glu5-MePhe8-MeGly9) SP (DiMe-C7) induce a Ca2+-dependent release of Met5-enkephalin (MET) from slices of periaqueductal gray matter (PAG) and striatum of rats. The MET release from striatal slices is greater than that from PAG slices because of the higher MET content of striatum. Intraventricular injection of SP and of the two related peptides induce analgesia in the rat, and their analgesic potency is in line with their capacity to release MET. Other neuropeptides which possess antinociceptive activity such as bombesin, neurotensin, vasopressin and somatostatin fail to release MET from PAG slices.

Animals↗

PubMed1982

Differential effects of D-Ala2 analogues of enkephalins on substance P-induced analgesia in rodents.

The systemic administration of subanalgesic doses of [D-Ala2, D-Leu5]enkephalin significantly potentiated the analgesia elicited in rats or mice by intraventricular injection of substance P. On the contrary, systemic administration of low doses of [D-Ala2,Met5]enkephalinamide antagonized the substance P-induced analgesia. The results support the notion of different physiological functions for the enkephalins and suggest an integrated role for enkephalins and substance P in the control of pain at supraspinal levels.

Animals↗

PubMed1982

Analgesic activity of substance P in rats: apparent mediation by met-enkephalin release.

The intracerebroventricular administration of Substance P (SP) produced a marked and short-lasting increase in the threshold for vocalization and vocalization afterdischarge in the rat after electrical stimulation of the tail. This effect was blocked by naloxone and potentiated by bacitracin, a peptidase inhibitor. The analgesic effect of SP was also blocked by the concomitant intraventricular injection of the specific antibody against the opioid peptide metenkephalin but not by the antibody against beta-endorphin. Anti-met-enkephalin did not block other pharmacological actions of SP. The results suggest that SP produces an analgesic effect in rats by releasing met-enkephalin at supra-spinal levels involved in pain control.

Analgesia↗

PubMed1982

Blockade by met-enkephalin antiserum of analgesia induced by substance P in mice.

In the tail-flick test in mice, the intraventricular administration of Substance P (10-5,000 ng/mouse) produced a naloxone-reversible analgesic effect of rapid onset and long duration. The dose-response curve was bell-shaped, the analgesic effect being smaller after the largest doses. The analgesia was blocked by concomitant intraventricular administration of the antibody against met-enkephalin but not by the antibody against beta-endorphin. In the hot plate assay, Substance P produced analgesia in mice with high sensitivity to pain, and hyperalgesia in mice with lower sensitivity to pain than normal. The analgesia was blocked by the antibody against met-enkephalin but the hyperalgesia or the scratching response were not modified by the antiserum. The results appear to indicate a dual effect, analgesic or hyperalgesic, of Substance P in mice, the former probably being mediated by release of met-enkephalin.

Analgesics↗

PubMedDate not supplied

Antinociceptive and Met-enkephalin releasing effects of tachykinins and substance P fragments.

Substance P (SP), physalaemin, SP4-11, SP5-11 and the SP5-11 analog DiMe-C7 induce an antinociceptive effect in rats after intraventricular administration. Other tachykinins and the N-terminal fragments of SP are inactive. All antinociceptive peptides increase the Met-enkephalin efflux from slices of rat periaqueductal gray matter and their antinociceptive potency is correlated with their capacity to release Met-enkephalin. The results, discussed in the light of current theories on different tachykinin receptors, suggest that the SP-P receptor subtype may be involved in the control of noxious stimulation elicited by SP at supraspinal levels.

Analgesics↗

PubMedDate not supplied

Antinociceptive effects in rodents of the dipeptide Lys-Trp (Nps) and related compounds.

Intracerebroventricular administration of the synthetic dipeptide derivative Lys-Trp (Nps) (LTN) elicits a potent and naloxone-sensitive antinociceptive effect in mice and in rats using heat and electrical current respectively as the noxious stimuli. LTN does not induce analgesia by directly acting on opioid receptors but the peptidase inhibiting activity of the new compound may account in part for the behavioral effect. LTN produces also a marked decrease in the met-enkephalin content of the periaqueductal gray suggesting a possible enkephalin releasing property. Structure-activity studies with different analogs of LTN indicate that replacement of Lys by other basic amino acids results also in compounds with a potent antinociceptive effect whereas replacement by neutral or acidic amino acids leads to a complete loss of activity.

Analgesia↗

PubMedDate not supplied

Extraction of peptides from guanidine thiocyanate homogenates used to isolate RNA.

A method is described in which the concentrated tissue extract that remains after preparation of RNA in guanidine thiocyanate can be salvaged for simultaneous measurements of neuropeptides by RIA and other neuroactive factors by bioassay. This procedure may be used for assessing alterations in tissue peptide content in addition to mRNA changes in the same tissue sample.

Animals↗

PubMedDate not supplied

Expression of cholecystokinin and enkephalin mRNA in discrete brain regions.

The levels of preprocholecystokinin mRNA were measured in several regions of rat brain using RNA blot analysis. In both species, high levels of expression were observed in the thalamus, amygdala, neocortical areas and hippocampus. Intermediate levels were observed in the periaqueductal grey, hypothalamus, substantia nigra, ventral tegmental area, and olfactory bulbs; little or no mRNA was detected in the caudate nucleus, nucleus accumbens, olfactory tubercle, cerebellum or a liver control. In contrast, the caudate and olfactory tubercle expressed large amounts of preproenkephalin mRNA. Other regions, such as the periaqueductal grey and olfactory bulbs, expressed both transcripts while regions like the hippocampus contained prominent amounts of preprocholecystokinin mRNA and relatively little preproenkephalin mRNA.

Actins↗