European journal of pharmacology
-
Orphanin FQ, also known as nociceptin, is a heptadecapeptide with very high affinity for a novel member of the cloned opioid receptor family which produces hyperalgesia in mice. In addition to hyperalgesia, which is observed soon after administration of orphanin FQ, we now describe a delayed analgesic response. Unlike orphanin FQ-induced hyperalgesia, orphanin FQ-induced analgesia is readily reversed by the opioid antagonist naloxone, implying an opioid mechanism of action. In view of the very poor affinity of orphanin FQ for all the known traditional opioid receptors and the low affinity of opioids for the 125I[Tyr14]orphanin FQ binding site, orphanin FQ-induced analgesia is probably mediated through a novel orphanin FQ receptor subtype.
-
Our previous work has suggested that the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) can abolish the protective effect of ischemic preconditioning in the isolated rat heart. Therefore we tested the hypothesis that CGRP- or capsaicin-induced preconditioning protects against ischemia-reperfusion injury in the isolated perfused rat heart. Thirty minutes of global ischemia and 30 min of reperfusion caused a significant cardiac contractile dysfunction, ventricular arrhythmia, and an increased release of creatine phosphate kinase. ⋯ However, the cardioprotection provided by CGRP- or capsaicin-induced preconditioning was abolished by CGRP-(8-37) and ruthenium red, respectively. These findings suggest that CGRP- or capsaicin-induced preconditioning protects against ischemic myocardial injury. The present results also suggest that CGRP may be an endogenous myocardial protective substance in the rat.
-
The effects of 2 antimigraine drugs sumatriptan and dihydroergotamine on dilatation of the middle meningeal artery elicited by stimulation of the trigeminal ganglion at the entry point of the first and second divisions was investigated in cats. Carotid and middle meningeal arterial blood flows and resistances were measured in 9 cats anesthetised with chloralose. Electrical stimulation of either trigeminal ganglion produced a frequency-dependent decrease in resistance of the carotid artery ipsilaterally and the middle meningeal artery bilaterally. ⋯ The intravenous injection of dihydroergotamine produced a larger and more prolonged vasoconstriction in these 2 beds than did sumatriptan. Dihydroergotamine, but not sumatriptan, blocked some components of the vascular response induced by stimulation of the trigeminal ganglion. Dihydroergotamine and sumatriptan have a different spectrum of activity on cranial circulatory beds and neither of them is able to reduce trigeminal-induced vasodilatation by blocking antidromic activation of trigeminal nerve fibres in cats at the doses used in these experiments.