PRESENCE AND BIOLOGICAL-ACTIVITY OF C-TYPE NATRIURETIC PEPTIDE-DEPENDENT GUANYLATE CYCLASE-COUPLED RECEPTOR IN THE PENILE CORPUS CAVERNOSUM

Purpose: To investigate the presence of C-type natriuretic peptide 1-2 2 (CNP)-dependent guanylyl cyclase (GC)-coupled receptor and its biolo gical function in the penile erectile smooth muscle, Materials and Met hods: Experiments have been done in rabbit and rat to detect cyclic GM P (cGMP) generation by the activation of particulate GC by natriuretic peptides (NPs) in cavernosal membrane, to localize precise receptor u sing a quantitative in vitro autoradiography of the snap frozen sectio ns, to define natriuretic peptide receptor (NPR) mRNA using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to moni tor changes of erectile smooth muscle tone by NPs in the penile tissue strips. Results: Productions of cGMP by particulate GC in the corpus cavernosum membranes of rabbit and rat were stimulated by CNP, atrial natriuretic peptide 1-28 (ANP) and brain natriuretic peptide 1-26 (BNP ) with a rank order of potency of CNP > BNP > ANP. HS-142-1, a selecti ve antagonist for the GC-coupled NPR, inhibited the CNP-stimulated cGM P production in corpus cavernosal membrane of rabbit and rat. Specific I-125-[Tyr(0)]-CNP bindings were localized in the corpus cavernosal s mooth muscle of rabbit with K-d, of 19.92 +/- 3.38 nM. and B-max of 73 4.64 +/- 139.63 amol./mm(2). B-subtype of NPR mRNA was detected in the penile corpus cavernosum of rat using RT-PCR technique. CNP relaxed t he smooth muscle contracted by N omega-nitro-L-arginine methylester (L -NAME). Conclusions: These results suggest for the first time that CNP modulates the erectile smooth muscle tone of penis by predominant act ivation of B-subtype of NPR with augmentation of cGMP production via p articulate GC.