Development of morphine-like physical dependence of the [D-Arg2, beta-Ala4]-dermorphin tetrapeptide (H-Tyr-D-Arg-Phe-beta-Ala-OH) has been evaluated and compared with the physical dependence liability of morphine or pentazocine. Degree of the physical dependence was assessed by the naloxone-precipitated jumping behaviour in mice after treatment of a single dose of each compound. The number of jumps and the time of latency to first jump were recorded in this experiment. Number of jumps in a group pretreated with the peptide showed less than that in morphine-treated group. In addition, latency to the appearance of the first jump in the peptide-treated mice was later than that in the morphine-treated group. The present results indicate that the physical dependence induced by [D-Arg2, beta-Ala4]-dermorphin tetrapeptide may be less marked than that produced by morphine. It is also interesting to note that the antinociceptive effect of this opioid peptide is more powerful and of longer duration than that induced by morphine or pentazocine.

Analgesics, Opioid↗

PubMedDate not supplied

Actions of intracerebroventricular administration of kyotorphin and an analog on thermoregulation in the mouse.

Intracerebroventricular (ICV) administration of kyotorphin (L-Tyr-L-Arg) and cyclo (N-methyl-L-Tyr-L-Arg), its analog, produced significant dose-dependent hypothermic responses in mice at an ambient temperature of 24 degrees C. The hypothermic action of kyotorphin was much greater than that of Met-enkephalin (Met-ENK) but less than that of cyclo NMTA. This action was slightly but not significantly reversed by intraperitoneally administered naloxone (8 mg/kg), an opioid receptor antagonist. Met-ENK utilized as a control peptide in this study also produced a dose-dependent hypothermia which was slightly antagonized by naloxone (8 mg/kg, IP). Thyrotropin releasing hormone (TRH) injected ICV produced hyperthermia dose-dependently. The hypothermia induced by kyotorphin, its cyclic analog and Met-ENK was prevented by a small dose of TRH (0.18 microgram = 0.5 nmol/animal) which by itself had little effect on body temperature. A TRH neuronal system in the brain may explain the mechanism of kyotorphin-induced hypothermia. However, there was little evidence of involvement of opioid receptors. The present study demonstrates a potent action of kyotorphin and its analog on thermoregulation.

Analgesics↗

PubMedDate not supplied

A comparison of the antinociceptive and behavioral effects of D-Arg substituted dipeptides and tetrapeptides in mice.

Intracerebroventricular administration of D-Arg substituted dipeptides, H-Tyr-D-Arg-OMe and H-Tyr(Et)-D-Arg-OMe, and D-Arg2 substituted N-terminal tetrapeptides of dermorphin, H-Tyr-D-Arg-Phe-Gly-OEt and H-Tyr(Et)-D-Arg-Phe-Gly-OEt resulted in dose-related and naloxone-reversible antinociceptive effects. Among them, tetrapeptides not only exhibited much more potent and prolonged activities than dipeptides but also were significantly antagonized even by a low dose of naloxone. Spontaneous motor activity was lowered by dipeptides throughout the observation period, which was scarcely antagonized by naloxone. Tetrapeptides elicited locomotor hyperactivity following an initial locomotor suppression. Only the locomotor hyperactivity was significantly antagonized by naloxone. These results suggest that tetrapeptides induce the effects via opioid receptors, whereas the effects of dipeptides are involved in various systems non-specifically.

Animals↗

PubMedDate not supplied

Antinociceptive cross-tolerance between [D-Arg2]-dermorphin tetrapeptide analogs and morphine.

Cross-tolerance between [D-Arg2]-dermorphin tetrapeptide analogs and morphine with respect to antinociception was examined in the present set of experiments. Systemic administration of H-Tyr-D-Arg-Phe-Gly-NH2 (TDAPG-NH2), H-Tyr-D-Arg-Phe-beta-Ala-OH (TDAPA) or morphine over a period of 5 days produced the development of tolerance. In the cross-tolerance study, antinociception after subcutaneous (SC), intracerebroventricular (ICV) and intrathecal (IT) administrations of TDAPG-NH2 and TDAPA in morphine-tolerant mice was not significantly different from their respective effects in saline-pretreated control mice. A marked tolerance to SC- and ICV-administered morphine was seen in mice made tolerant to TDAPG-NH2 and TDAPA. However, IT administration of morphine produced no significant decrement in the antinociceptive activity in mice made tolerant to TDAPG-NH2 and TDAPA. These data indicate that [D-Arg2]-dermorphin tetrapeptide analogs can produce significant antinociception in morphine-tolerant mice.

Amino Acid Sequence↗

PubMedDate not supplied

A case of thyrotropin (TSH)-secreting tumor complicated by periodic paralysis.

A 27-year-old man had symptoms of hyperthyroidism and periodic paralysis. While hyperthyroid, his serum thyrotropin (TSH) level was inappropriately elevated at 6.4 microU/ml. The serum alpha subunit level was also elevated. MR imaging revealed a pituitary tumor and transsphenoidal adenomectomy was performed. Immunocytochemistry with an antibody directed against the beta-subunit of TSH revealed a TSH-secreting tumor. This is the first case of hyperthyroidism due to a TSH-secreting pituitary tumor complicated by periodic paralysis. This association indicates that thyrotoxicosis may induce paralysis in susceptible persons by a mechanism which is not autoimmune.

Adenoma↗

PubMedDate not supplied

Effect of perilymphatic air perfusion on cochlear potentials.

Perilymphatic fistula is now widely recognized to cause acute profound hearing loss. It is still controversial, however, which mechanism it is that causes the reversible hearing loss. Recently, it has been suggested by two groups of researchers that the intrusion of air bubbles into the perilymphatic space (a condition called pneumolabyrinth or aerolabyrinth) through the ruptured labyrinthine window(s) may be one of the causes. In order to examine the mechanism underlying the hearing loss associated with pneumolabyrinth, the perilymphatic space of the guinea pig cochlea was perfused with air and cochlear potentials were recorded. Although perfusion of the scala tympani with air at a rate as high as 200 microliter/min caused an immediate and drastic decrease of the cochlear microphonics (CM) and the compound action potential (AP), it had little effect on the endocochlear dc potential (EP) during perfusion for 20 min. A decline in EP was seen in half the ears, but only when the duration of perfusion exceeded 30 min. These results show that the EP has an amazing resistance to air trapped in the scala tympani of the cochlea and that the initial decrease of hearing acuity after the elimination of perilymph from the scala tympani (or introduction of air into the scala tympani) is probably due to interference in CM and AP generation mechanisms rather than to strial dysfunction.

Action Potentials↗