Pharmacology & Toxicology Poster Session

Carla Cioni

>Great poster.  Is there any homologue or comparable vasoactive peptides to urotensins in higher organisms?  Also, you've identified a role for NO production in these fish- which in turn, regulates the production of these urotensins- NO in higher organisms, seems to function primarily as a vasodilator, some reports of vasoconstrictor effects (associated with peroxinitrite, maybe), seems like a complex issue in the fish, not as linear.  Any thoughts of NOS fish knockouts?!?!?

>Regards,
>Christopher Tan

Dear Dr. Tan,
sorry for the long delay in answering, but I'm having a lot of trouble with the Internet connection! May be one of my colleagues succeded in contacting you last days.
First of all, thanks for your suggestions. Yes. As Dr. De Vito wrote, urotensins I and II have homologues in higher vertebrates. Beyond mammalian CRF and frog sauvagine, UI is also structurally similar to urocortin, a peptide recently identified in the rat brain, which shares 63% of its sequence with fish UI. On the other hand, UII cannot be considered the piscine equivalent of mammalian somatostatin-14, because fish contain high concentrations of authentic somatostatin-14. UII has been demonstrated also in the frog brain. However, no evidence is still available for the existence of UII-related peptides in birds, reptiles or mammals. Nevertheless, fish UII is able to produce hypothensive response in rat. It has been suggested that the hypothensive response is mediated via the synthesis of nitric oxide and prostaglandins. Thus, NO production might mediate the biological activity of urotensins. As you can see, it's a complex issue in the fish too.

In our work we characterized a simple model to study the role of NO in neuroscretion. Results obtained suggest that the modulatory role of NO in neuroendocrine regulation appears early in the vertebrate evolution. We suggest that NO is produced in the axon terminals in response to a definite (osmotic?) stimulus. NO stimulates the release of urophysial hormones by exocitosis of the neurosecretory granules. NO then diffuse to mediate the short-range communication between activated and non-actived terminals. In this model, we propose that NO play a central role in the coordination of urotensin release.
This hypothesis, however, still remains to be demonstrated.

I've never heard about transgenic fish NOS knockouts. Do you? I appreciated if you let me know.

My best,

Carla Cioni.