Role of arginase in the male and female sexual arousal response

Abstract

The NO-cGMP pathway plays a key role in the male and female genital sexual arousal response. Nitric oxide synthase (NOS) utilizes L-arginine and oxygen as substrates to produce nitric oxide (NO) and citrulline. Arginase is a metalloenzyme that catalyzes the hydrolysis of L-arginine to produce L-ornithine and urea. It is proposed that arginase competes for L-arginine and reduces NOS activity in genital tissues, thus modulating sexual function. Using 2 transition state analogue inhibitors of arginase, 2(S)-Amino-6-boronohexanoic acid (ABH) and S-(2-boronoethyl)-L-cysteine (BEC), we have characterized arginase activity in penile and vaginal tissue. Neither of these inhibitors has activity against NOS. Thus, ABH and BEC are useful compounds for examining the role of arginase in genital tissue physiology, without directly influencing NOS activity. We present data to suggest that arginase may regulate NO production by competing for endogenous pools of L-arginine. In this fashion, arginase is an indirect regulator of penile and vaginal blood flow and specific arginase inhibitors may improve genital blood flow during sexual arousal. As evidenced by the upregulation of arginase in specific disease states, its distribution in the vagina, and its modulation by sex steroid hormones, this enzyme may also participate in numerous other physiological and pathophysiological processes, such as tissue growth, fibrosis, and immune function.