Erections normally occur at the time of physical or mental sexual stimulation which leads to an increase in blood flow to the erectile tissues in the penis. In addition, a decreased outflow of blood from the penis (venous outflow) occurs which maintains the rigidity of the erectile tissues during sexual activity. The vascular response is a consequence of nerves within the erectile tissues producing a chemical (cyclic GMP or cGMP) that decreases resistance of blood inflow to the penis. The penile tissues also produce an enzyme, phosphodiesterase-5 (or PDE-5) that degrades the cGMP, reversing the increase in blood inflow. PD-5 is blocked by a class of medications known as PDE-5 inhibitors (including Viagra, Cialis, and Levitra) thereby slowing the degradation of cGMP and, consequently, promoting and sustaining the erection. However, the response to these medications depends upon the primary sexual stimulation that initiates the increase cGMP release.
cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular smooth muscles lead to vasodilation and increased blood flow.
cGMP is a secondary messenger in phototransduction in the eye. In the photoreceptors of the mammalian eye, the presence of light activates phosphodiesterase, which degrades cGMP. The sodium ion channels in photoreceptors are cGMP-gated, so degradation of cGMP causes sodium channels to close, which leads to the hyperpolarization of the photoreceptor’s plasma membrane and ultimately to visual information being sent to the brain. GMP and a number of its derivatives also have an umami taste.
cGMP is also seen to mediate the switching on of the attraction of apical dendrites of pyramidal cells in cortical layer V towards semaphorin-3A. Whereas the axons of pyramidal cells are repelled by Sema3a, the apical dendrites are attracted to it. The attraction is mediated by the increased levels of soluble guanylate cyclase (SGC) that are present in the apical dendrites. SGC generates cGMP, leading to a sequence of chemical activations that result in the attraction towards Sema3a. The absence of SGC in the axon causes the repulsion from Sema3a. This strategy ensures the structural polarization of pyramidal neurons and takes place in embryonic development.