Julian Dow GBAA02 at
Fri Sep 2 09:14:24 EST 1994

In article <345eam$ea4 at>, mpm at (Mark Mattson)

> : My question is: Does it not sound strange measuring cGMP outside living cells?
> : Shouldn't cGMP be found only inside the cells, except following cell disruption
> : or membrane damage?> There is 
> substantial evidence that cGMP and cAMP are released from cells; in some
> systems, as much as two-thirds of the cGMP synthesized gets out.
> I don't have refs at hand, but I know Ron Fiscus has published some 
> studies on cyclic nucleotides released from cultured cells.

Remember, cyclic GMP was first characterised as a secreted product in
In the insect version of the kidney, the Malpighian tubules, both cAMP and
cGMP seem able to scoot through both basal and apical sides of the

Ref for cyclic AMP : Coast, G. M., Cusinato, O., Kay, I., and Goldsworthy,
G. J. (1991). An evaluation of the role of cyclic AMP as an intracellular
second messenger in Malpighian tubules of the house cricket, Acheta
domesticus. Journal of Insect Physiology 37, 563-573.

In fact, external cGMP can stimulate tubules at *extracellular* levels as
low as 10 micromolar! Ref: Dow, J. A. T., Maddrell, S. H. P., Davies,
S.-A., Skaer, N. J. V., and Kaiser, K. (1994). A novel role for the nitric
oxide/cyclic GMP signalling pathway: the control of fluid secretion in
Drosophila. American Journal of Physiology 266, R1716-R1719.

Our guess is that cyclic nucleotides are hitching a ride on a transporter
that's designed for the excretion of small organic ions. It's interesting
that a cell can use as a second messenger a molecule to which its p.m. is
freely permeable!

On a broader phylogenetic basis, recall also that Dictyostelium uses
deliberate secretion of cAMP as a cheoattractant in grex formation (see
Alberts 3rd ed. pp 831-2).

 - Julian Dow

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