The contributions of μ‐, δ‐and κ‐opioid receptors to the actions of endogenous opioids on spinal reflexes in the rabbit

Open Access
Publisher Website
Google Scholar
Abstract
1 Spinal reflexes in the rabbit are suppressed tonically by endogenous opioids. The contributions made to this suppression by μ-, δ-and κ-opioid receptors have been investigated by studying the actions of a range of opioid antagonists and agonists on reflexes evoked by sural nerve stimulation in the ankle extensor gastrocnemius medialis (g.m.), and in the knee flexor semitendinosus (s.t.). 2 When given at a total dose of 88.5 μg kg−1 i.v., either of the universal opioid receptor antagonists (–)-naloxone and (–)-quadazocine enhanced the g.m. response to more than 7 times the pre-drug control values, and the s.t. reflex to 1.5 times controls. The effects of quadazocine were stereospecific. The selective δ antagonist ICI 174864 (3.5 mg kg−1 i.v. total) also augmented the g.m. reflex but only to twice pre-drug controls. 3 The μ-agonists fentanyl (100 μg kg−1) and morphine (50 mg kg−1) suppressed both g.m. and s.t. reflex responses to less than half control levels by a naloxone-reversible mechanism. 4 The κ-agonists bremazocine (50 μg kg−1 total), tifluadom (100 μg kg−1), ethylketocyclazocine (200 μg kg−1) and U50488H (1 mg kg−1) potentiated the g.m. reflex and had variable effects on the s.t. response. Naloxone usually added to the facilitatory actions of these drugs. κ-Opioid receptor agonists also caused a profound, naloxone-reversible depression of arterial blood pressure. 5 It may be concluded that the endogenous opioid-mediated suppression of spinal reflexes in the rabbit is mediated mainly, if not exclusively, through μ-receptors. There are no known endogenous ligands which are specific for the μ-receptor, so in the present case it seems that selectivity is determined by the receptor population rather than by the ligand.