The endothelin ET(B) receptor agonist [125I]BQ-3020 binds predominantly to nerves in the bovine retractor penis muscle and penile artery.
Preliminary pharmacological experiments have suggested that in the bovine retractor penis muscle there are relaxation-mediating endothelin ET(B) receptors, at least part of which are located on the inhibitory nitrergic nerves. The present work was undertaken to test this hypothesis by means of receptor autoradiography and additional pharmacological experiments. In the retractor penis muscle and the penile artery, specific binding of the ETB receptor-selective agonist [125I]BQ-3020 took place predominantly to nerve trunks and minor nerve branches. The situation was the same in the dorsal metatarsal artery, that was included as a reference because of its different innervation. Throughout the nerves the silver grains were evenly distributed over the nuclei of Schwann cells and the spaces between them. In the retractor penis there was also a small amount of specific binding to smooth muscle. No specific endothelial binding was observed in any of the tissues examined. The pharmacological studies confirmed that the relaxation of the retractor penis muscle induced by the ET(B) receptor-selective agonist, sarafotoxin S6c, is susceptible to tetrodotoxin as well as to inhibition of nitric oxide synthase. The relaxation was also characterized by inconsistency, weakness and tachyphylaxis. The electrical field stimulation-induced submaximal relaxation of the retractor penis was unaffected by stimulation or blockade of ET(B) receptors. The autoradiography suggests that in all the three bovine tissues studied there are ET(B) receptors located on nerves independently of the type of efferent nerve. The pharmacological experiments do not support the concept that in the bovine retractor penis muscle neuronal ET(B) receptors exert important immediate effects on the functioning of the penile erection-mediating nitrergic nerves.
Parkkisenniemi
U M
UM
Department of Pharmacy, University of Helsinki, Finland. Ulla-Mari.Parkkisenniemi@helsinki.fi
Palkama
A
A
Virtanen
I
I
Klinge
E
E
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D001345:Autoradiography; D002417:Cattle; D019334:Endothelin-3 / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism* / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010413:Penis / Q000098:blood supply / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D014757:Viper Venoms / Q000494:pharmacology
D019334:Endothelin-3; D016232:Endothelins; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; C075771:BQ 3020; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); C086539:BQ 788