Seminal plasma factors that cause large elevations in cellular cyclic GMP are C-type natriuretic peptides.

Seminal plasma (porcine) was shown to elevate cyclic GMP in Balb/3T3 cells (235-fold), NIH/3T3, Rat-2, but not in human T84 cells. Seminal plasma and C-type natriuretic peptide (CNP) markedly elevated cyclic GMP of 293 cells stably transfected with the guanylyl cyclase-B (GC-B) receptor, but failed to elevate cyclic GMP concentrations of 293 cells stably transfected with the guanylyl cyclase-A receptor. The seminal plasma activity was analyzed by reverse-phase high performance liquid chromatography; two major fractions were obtained and the amino acid sequence of one matched that of proCNP-103. For the second peak of activity, sequence could not be obtained but the purified material bound to antibody specific for CNP. CNP concentrations in seminal plasma and seminal vesicle fluid were shown to be 2,000- and 100,000-fold greater than those found in porcine brain, respectively. Significant amounts of immunoreactive CNP also were detected in tracheal mucosa and uterus suggesting a general signaling role for the peptide. That seminal plasma CNP serves a function during fertilization was suggested by finding expression of GC-B mRNA in the uterus/oviduct and CNP-stimulatable GC-B in the intact uterus. Therefore, some or all of the GC-B receptor appears to exist on the apical membrane of uterine epithelial cells.