Here we have a resolution on the biochemistry behind thesustainability of the penile erection and an obvious target fortherapy. Also an obvious target for drug company research I am sure.
The advent of drugs into this market did not provide an universallysuccessful solution at all but provided some a partial solution. This left plenty of room for improvement although most likely thinkthe problem is solved. Thus the continued press for researchsolutions.
The real problem is to find solutions which can work with otherpharmaceutical therapies that block the natural biochemistry. Thishas that promise.
RESEARCHERS UNCOVER BIOCHEMICAL CHAIN OF EVENTS NEEDED TOMAINTAIN AN ERECTION
Release Date:09/26/2012
Discovery in mice maylead to new therapies for men with erectile dysfunction
http://www.hopkinsmedicine.org/news/media/releases/researchers_uncover_biochemical_chain_of_events_needed_to_maintain_an_erection
For two decades,scientists have known the biochemical factors that trigger penileerection, but not what’s needed to maintain one. Now an article byJohns Hopkins researchers, scheduled to be published this week bythe Proceedings of the National Academy of Sciences(PNAS), uncovers the biochemical chain of events involved inthat process. The information, they say, may lead to new therapies tohelp men who have erectile dysfunction.
“We’ve closed agap in our knowledge,” says Arthur Burnett, M.D., professor ofurology at Johns Hopkins Medicine and the senior author of the studyarticle. “We knew that the release of the chemical nitric oxide, aneurotransmitter that is produced in nerve tissue, triggers anerection by relaxing muscles that allow blood to fill the penis. Wethought that was just the initial stimulus. In our research, wewanted to understand what happens next to enable that erection to bemaintained.”
In a study of mice,Burnett and his colleagues found a complex positive feedback loop inthe penile nerves that triggers waves of nitric oxide to keep thepenis erect. He says they now understand that the nerve impulses thatoriginate from the brain and from physical stimulation are sustainedby a cascade of chemicals that are generated during the erectionfollowing the initial release of nitric oxide. “The basic biologyof erections at the rodent level is the same as in humans,” hesays.
The key finding isthat after the initial release of nitric oxide, a biochemical processcalled phosphorylation takes place to continue its release andsustain the erection.
In a landmark studypublished in the journal Science in 1992, Burnett and hisJohns Hopkins co-author, Solomon S. Snyder, M.D., professor ofneuroscience (who is also an author on the current study), showed forthe first time that nitric oxide is produced in penile tissue. Theirstudy demonstrated the key role of nitric oxide as a neurotransmitterresponsible for triggering erections.
“Now, 20 yearslater, we know that nitric oxide is not just a blip here or there,but instead it initiates a cyclic system that continues to producewaves of the neurotransmitter from the penile nerves,” saysBurnett.
With this basicbiological information, it may be possible, according to Burnett, todevelop new medical approaches to help men with erection problemscaused by such factors as diabetes, vascular disease or nerve damagefrom surgical procedures. Such new approaches could be used tointervene earlier in the arousal process than current medicinesapproved to treat erectile dysfunction.
In particular, Burnettsays, “The target for new therapies would be the protein kinase A(PKA) phosphorylation of neuronal nitric oxide synthase (nNOS). Nowthat we know the mechanism for causing the ‘activated’ form ofnNOS in penile nerves, we can develop agents that exploit thismechanism to help with erection difficulties.”
One of the agentsstudied by the researchers was forskolin, an herbal compound that hasbeen used to relax muscle and widen heart vessels. They found thatforskolin also ramps up nerves and can help keep nitric oxide flowingto maintain an erection.
“It has been a20-year journey to complete our understanding of this process,”says Snyder. “Now it may be possible to develop therapies toenhance or facilitate the process.”
The new study, “CyclicAMP Dependent Phosphorylation of Neuronal Nitric Oxide SynthaseMediates Penile Erection,” was funded by the National Institute ofDiabetes and Digestive and Kidney Diseases (NIDDK), under grantnumber RO1DK067223.
In addition to Burnettand Snyder, the study article’s authors are K. Joseph Hurt from theUniversity of Colorado, Sena F. Sezen, Gwen F. Lagoda and BiljanaMusicki from Johns Hopkins, and Gerald A. Rameau from Morgan StateUniversity.
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