Effects of ethylketocyclazocine on adrenergic transmission in the isolated perfused cat spleen.
The pre- and postsynaptic effects of ethylketocyclazocine (EKC), a putative kappa opiate receptor agonist, on sympathetic adrenergic neurotransmission were investigated using the isolated perfused cat spleen. Perfusion of spleens with EKC (10(-7) and 10(-6)M) produced a modest dose-dependent inhibition of nerve-stimulation-mediated overflow of norepinephrine (NE) and total 3H. In contrast, EKC (10(-4)M) produced an increase in the release of NE, and total 3H overflow. Perfusion with EKC (10(-5) and 10(-4)M) resulted in a dose-dependent inhibition of the postsynaptic response to stimulation-mediated release of NE. Likewise, EKC inhibited splenic contraction due to exogenously administered NE which was not antagonized by naloxone. These results suggest that EKC exerts a direct effect on peripheral adrenergic neurotransmission not mediated via classical kappa opiate receptors.
Gaddis
R R
RR
Dixon
W R
WR
D000818:Animals; D002415:Cats; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D016314:Ethylketocyclazocine; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D010477:Perfusion; D011957:Receptors, Opioid / Q000502:physiology; D017473:Receptors, Opioid, kappa; D013154:Spleen / Q000187:drug effects* / Q000294:innervation; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D016314:Ethylketocyclazocine; D003496:Cyclazocine; D009638:Norepinephrine