Functional characterization of nonadrenergic noncholinergic neurotransmitter release via endocannabinoids: an in vitro study in rabbit corpus cavernosum.
BACKGROUND
Corporal smooth muscle relaxation is mediated mainly but not completely by nitric oxide. Endocannabinoids modulate the various neurotransmitter systems.


OBJECTIVE
In the present study, a possible role of endocannabinoids on non-nitrergic nonadrenergic noncholinergic (NANC)-mediated relaxations was investigated.


METHODS
In precontracted tissues, control electrical field stimulation (EFS)-induced NANC relaxation responses were obtained using varying frequencies of stimulation in the presence of L-arginine methyl ester (L-NAME), guanethidine, and atropine. To investigate the effects of cannabinoids on EFS-evoked non-nitrergic NANC relaxation responses, a similar experimental procedure was applied in the presence of cannabinoid receptor antagonists AM251 or AM630; vanilloid receptor antagonist capsazepine; or cannabinoid receptor agonists anandamide, arachidonyl-2-chloroethylamide (ACEA), or JHW015.


METHODS
Effects of cannabinoid receptor antagonists and agonists on EFS-evoked non-nitrergic NANC relaxation responses.


RESULTS
L-NAME abolished EFS-induced relaxation responses at lower frequencies (2-4 Hz) and inhibited the relaxation responses at higher frequencies (8-32 Hz). AM251 and AM630 either together or separately inhibited, whereas anandamide, ACEA, and JHW015 enhanced non-nitrergic NANC relaxation responses. Anandamide did not alter EFS-induced non-nitrergic NANC relaxations in the presence of AM251 and AM630. Capsazepine enhanced non-nitrergic NANC relaxation responses.


CONCLUSIONS
These results suggest that non-nitrergic NANC relaxations may be mediated partially by cannabinoid-like neuronal factors acting at both cannabinoid CB(1) and cannabinoid CB(2) receptors.
Vural
Ismail M
IM
Department of Pharmacology, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
Ozturk
Gokce S
GS
Sarioglu
Yusuf
Y
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D015153:Blotting, Western; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation / Q000379:methods; D063388:Endocannabinoids; D006145:Guanethidine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010276:Parasympatholytics / Q000008:administration & dosage / Q000494:pharmacology; D010413:Penis / Q000187:drug effects*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013565:Sympatholytics / Q000008:administration & dosage / Q000494:pharmacology
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D010276:Parasympatholytics; D053284:Polyunsaturated Alkamides; D011950:Receptors, Cholinergic; D013565:Sympatholytics; D009569:Nitric Oxide; D001285:Atropine; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester; D006145:Guanethidine