8 research outputs found
Dermorphin tetrapeptide誘導体Tyr-D-Arg-Phe-β-AlaおよびTyr-D-Arg-Phe-β-Ala-NH_2の鎮痛作用発現におけるμ1受容体の関与
Involvement of μ1-opioid receptor on the antinociception induced by dermorphin tetrapeptide analogues Try-D-Arg-Phe-β-Ala (TAPA) and Tyr-D-Arg-Phe-β-Ala-NH_2 (TAPA-NH_2) were determined in mice, using a tail-pressure test and formalin test. TAPA and TAPA-NH_2 injected i. c. v. and i. t. produced dose-dependent antinociception in both assays. In the tail-pressure test, the antinociception induced by i. c. v. and i. t. injected TAPA, but not TAPA-NH_2, was significantly attenuated by the pretreatment with naloxonazine, selective antagonist for μ1-opioid receptor. Moreover, naloxonazine also significantly attenuated the antinociception induced by i. c. v. injected TAPA, but not TAPA-NH_2 in formalin test. In contrast, the antinociception induced by both TAPA and TAPA-NH_2 given i. t. was significantly attenuated by the pretreatment with naloxonazine in formalin test. The present results suggest that TAPA and TAPA-NH_2 should be considered to be selective agonist for μ1-and μ2-opioid receptors, respectively. The C-terminal amidation may be the critical portion for TAPA-NH_2 to distinguish μ1-and μ2-opioid receptors
Endomorphin analogues containing D-Pro(2) discriminate different μ-opioid receptor mediated antinociception in mice
The antagonistic actions of D-Pro(2)-endomorphins on inhibition of the paw withdrawal response by endomorphins were studied in mice. D-Pro(2)-endomorphin-1 and D-Pro(2)-endomorphin-2, injected intrathecally (i.t.), had no significant effect on the nociceptive thermal threshold alone. When D-Pro(2)-endomorphin-1 (0.05–0.1 pmol) was injected simultaneously with i.t. endomorphin-1 (5.0 nmol) or endomorphin-2 (5.0 nmol), antinociception induced by endomoprhin-1 was reduced significantly, whereas endomorphin-2-induced antinociception was not affected by D-Pro(2)-endomorphin-1. Antinociception induced by i.t. endomorphin-2 (5.0 nmol) was reduced significantly by its analogue, D-Pro(2)-endomorphin-2 (100 pmol), but not by D-Pro(2)-endomorphin-1. D-Pro(2)-endomorphin-1. D-Pro(2)-endomorphin-1 also antagonized the antinociceptive effect of i.t. DAMGO, a μ-opioid receptor agonist, whereas D-Pro(2)-endomorphin-2 failed to reduce the effect of DAMGO. These results suggest that endomorphin analogues containing D-Pro(2) are able to discriminate the antinociceptive actions of μ(1)- and μ(2)-opioid receptor agonists at the spinal cord level
Nociceptin (1–7) antagonizes nociceptin-induced hyperalgesia in mice
Nociceptin and its N-terminal fragment, nociceptin (1–7), were administered intrathecally (i.t.) into conscious mice. Nociceptin (3.0 fmol) produced a significant reduction in the nociceptive thermal threshold (hyperalgesia) measured as the tail-flick and paw-withdrawal responses. Nociceptin (1–7), injected i.t., at 150–1200 fmol had no significant effect. However, when nociceptin (1–7) (150–1200 fmol) was injected simultaneously with nociceptin (3.0 fmol), nociceptin-induced hyperalgesia was significantly reduced. Analgesia induced by a high dose (1200 pmol) of nociceptin was not antagonized by co-administration of nociceptin (1–7) (1200 fmol). These results suggest that N-terminal fragments of nociceptin formed endogenously could modulate the hyperalgesic action of nociceptin in the spinal cord
Nociceptin-induced scratching, biting and licking in mice: involvement of spinal NK(1) receptors
1. Intrathecal (i.t.) injection of nociceptin at small doses (fmol order) elicited a behavioural response consisting of scratching, biting and licking in conscious mice. Here we have examined the involvement of substance P-containing neurons by using i.t. injection of tachykinin neurokinin (NK)(1) receptor antagonists and substance P (SP) antiserum. 2. Nociceptin-induced behavioural response was evoked significantly 5–10 min after i.t. injection and reached a maximum at 10–15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 0.375–30.0 fmol, and the maximum effect was observed at 3.0 fmol. 3. The behavioural response elicited by nociceptin (3.0 fmol) was dose-dependently inhibited by intraperitoneal (i.p.) administration of morphine. 4. The NK(1) receptor antagonists, CP-96,345, CP-99,994 and sendide, inhibited nociceptin-induced behavioural response in a dose-dependent manner. A significant antagonistic effect of [D-Phe(7), D-His(9)]SP (6–11), a selective antagonist for SP receptors, was observed against nociceptin-induced response. The NK(2) receptor antagonist, MEN-10376, had no effect on the response elicited by nociceptin. 5. Pretreatment with SP antiserum resulted in a significant reduction of the response to nociceptin. No significant reduction of nociceptin-induced response was detected in mice pretreated with NKA antiserum. 6. The N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK-801) and D(−)-2-amino-5-phosphonovaleric acid (APV) (D-APV), and L-N(G)-nitro arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, failed to inhibit nociceptin-induced behavioural response. 7. The present results suggest that SP-containing neurons in the mouse spinal cord may be involved in elicitation of scratching, biting and licking behaviour following i.t. injection of nociceptin