'Cross talk' between opioid peptide and adrenergic receptor signaling in isolated rat heart.
BACKGROUND
Cardiac myocyte sarcolemma contains both catecholamine and opioid peptide receptors (OPRs). Opioid peptides are coreleased with catecholamines from nerve terminals in the heart. We investigated whether OPR stimulation influences the effects of beta-adrenergic receptor (beta-AR) stimulation in the isolated, isovolumic rat heart and whether the mechanism of such an interaction involves both beta-AR subtypes or an alteration in beta-AR-mediated increase in cAMP.


RESULTS
Norepinephrine (NE, 10(-7) mol/L) increased peak left ventricular systolic pressure (LVSP) and cAMP more than twofold compared with controls. The delta-OPR agonist leucine-enkephalin (LE, 10(-8) mol/L) markedly inhibited the beta1-AR-induced positive inotropic effect and increase in cAMP but alone had no effect on basal LVSP or basal cAMP levels. The OPR antagonist naloxone 10(-8) mol/L added to LE+NE perfusate reversed the LE-induced decrease in cAMP and LVSP even though naloxone alone had no effect on LVSP and cAMP levels. LE could not counteract the twofold increase in LVSP produced by the nondegradable cAMP analog CPT-cAMP 2.3x10(-5) mol/L or a high concentration of forskolin (10(-7) mol/L) but did reverse the 173+/-11.8% and 135+/-13.6% increases in LVSP stimulated by 10(-8) and 0.5x10(-8) mol/L forskolin, respectively. LE inhibited cAMP production at all concentrations of forskolin (10(-7), 10(-8), and 0.5x10(-8) mol/L). Pertussis toxin (PTX) pretreatment abolished LE effects on beta1-AR stimulation. Zinterol 10(-5) and 10(-6) mol/L, a specific beta2-AR agonist that elicits a cAMP-independent inotropic effect in rat heart, caused 225+/-14% and 182+/-5% increases in LVSP that could not be reversed by addition of LE.


CONCLUSIONS
Potent, inhibitory "cross talk" between delta-OPR and beta1-AR signaling pathways occurs via a PTX-sensitive G(i/o) protein involved in adenylyl cyclase inhibition in rat heart.
Pepe
S
S
Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, Md 21224, USA.
Xiao
R P
RP
Hohl
C
C
Altschuld
R
R
Lakatta
E G
EG
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004743:Enkephalin, Leucine / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D013599:Systole / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists; D004983:Ethanolamines; D009292:Narcotic Antagonists; D011942:Receptors, Adrenergic, alpha; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D017465:Receptors, Opioid, delta; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D009270:Naloxone; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D004743:Enkephalin, Leucine; C002904:zinterol; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009638:Norepinephrine