Tonic opioid inhibition of the pressor region of the rostral ventrolateral medulla of rabbits is mediated by delta receptors.
From previous observations, we have suggested that an endogenous opioid input tonically inhibits the pressor neurons of the rostral ventrolateral medulla (RVLM) of rabbits. In the present studies, the specific opioid receptor subtype(s) which may be activated by such an endogenous innervation were examined using local administration of selective antagonists. The RVLM pressor region of chloralose-anesthetized and artificially ventilated rabbits was functionally identified by local administration of L-glutamate (5 nmol). Selective blockade of neither mu nor kappa receptors in the RVLM after bilateral injections of beta-funaltrexamine (300-900 pmol) or nor-binaltorphimine (1 nmol), respectively, had any effect on either mean arterial pressure or heart rate. Delta receptors were blocked with ICI 174,864 (30-300 pmol). After the highest dose, there was a significant pressor effect (+32 +/- 6 mm Hg, mean +/- S.E.), which was of immediate onset and rapid time course (approximately 15 min), and which was accompanied by a bradycardia. In contrast, vehicle injections or injection of an inactive analog (ICI 178,173) had no effects. These results, together with previous pharmacological and anatomical evidence, suggest that there exists an enkephalinergic input to the RVLM that tonically inhibits the presympathetic pressor neurons via activation of delta-opioid receptors.
Morilak
D A
DA
Department of Medicine, Flinders Medical Centre, Bedford Park, South Australia.
Drolet
G
G
Chalmers
J
J
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D008845:Microinjections; D009271:Naltrexone / Q000031:analogs & derivatives; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects*; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D004745:Enkephalins; D005971:Glutamates; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid; D004743:Enkephalin, Leucine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C024524:beta-funaltrexamine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine