The cardiovascular and renal effects of a highly potent mu-opioid receptor agonist, cyclo[N epsilon,N beta-carbonyl-D-Lys2,Dap5]enkephalinamide.
Investigation of the acute cardiovascular and renal effects of cyclo[Nepsilon,Nbeta-carbonyl-D-Lys2,Dap5]enkephalinamide (cUENK6), the most potent mu-opioid receptor agonist, revealed dose-related effects, but most pronounced during the first hour post i.v. injections. During first hour, cUENK6 (3 microg/rat) stimulated (P<0.001) excretion of urine (1.1+/-0.2 vs. 3.3+/-0.3 ml/h), sodium (60+/-10 vs. 124+/-12 microeq/h), potassium and cGMP (1.76+/-0.19 vs. 4.92+/-0.80 nmol/h). These effects were inhibited by naloxone (4 mg/kg i.v.), but not by naloxonazine (35 mg/kg s.c.), or 4 mg/kg i.v. naloxone methiodide. cUENK6 stimulated urinary atrial natriuretic peptide (ANP)-like activity (113+/-12 vs. 167+/-20 pg/h, P<0.02) and the effect was totally abolished by naloxone. cUENK6 also suppressed the transient stress-induced elevation in blood pressures and heart rate that occurred over the first 30-min post-injection, an effect attenuated by naloxone. Plasma ANP increased 2-h post-injection (123+/-11 vs. 192+/-21 pg/ml, P<0.005), and was associated with augmented ANP mRNA levels in right atria and left ventricles. Thus, cUENK6 evokes renal effects by enhancing activity of the renal natriuretic peptide system.
Laboratory of Peptides, Department of Chemistry, University of Warsaw, Warsaw, Poland.
Jolanta
J
Gutkowska
Marek
M
Jankowski
Danuta
D
Pawlak
Suhayla
S
Mukaddam-Daher
Jan
J
Izdebski
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology
D004745:Enkephalins; D017450:Receptors, Opioid, mu; C107672:enkephalinamide, cyclo(N,N'-carbonyl-lysyl(2,5))-; D009270:Naloxone