I've noticed that as soon as water is applied to the Kambo it goes a bit orange as you noticed. I reckon it must be some kind of oxidation process, but it doesn't seem to affect the potency of the Kambo. I have wet the Kambo on my stick and it still affects me after it's gone orange.
What I think is that the Kambo dot slowly releases the bioactive peptides through the water, ie. they are water soluble (hence why it dissolves into the blood). If the water touches something, like skin, then the peptides can be transferred (via Brownian motion). If the water doesn't, then it simply dehydrates and the Kambo retains the peptides.
I believe that wetting the dots when in contact with the skin helps to continue spreading the Kambo peptides that haven't been in contact with the skin. Presumably there is still a fair amount of active ingredient in used Kambo (in the centre of the dot), though less than the original.
I liken it to a tea bag. Put it into a cup of boiling water once, and it will give you a dark cup of tea. Use the same tea bag twice, and you will get another cup of tea, but a bit more dilute. Use it a third time and it starts to really be dilute but you still get something from it. I assume that Kambo is the same. Use it a second time after moving it around in water, thereby exposing new surface area, and it will give you another hit, but with only partial potency.
All conjecture. We need us a guinea pig!