OFFICE MEMORANDUM e@ STANFORD UNIVERSITY @ OFFICE MEMORANDUM e@ STANFORD UNIVERSITY @ OFFICE MEMORANDUM

To

FROM

SUBJECT:

Date: September 16, 1975

Dr. Joshua Lederberg
Gary M. Gray, Md. @ D+-l .

Potential Use of Cholera Toxin for Treatment of Serious Constipation in
: : . TS Rin
Diverticulitis.

Dear Professor Lederberg:

I sincerely, regret the long delay in responding to your memo regarding
this subject. But I wanted to give it some thought before answering. Cholera
toxin appears to act by stimulating adenylttyclase to synthesize cyclic AMP
which in turn stimulates the active secretion of chloride ion. As far as we
know at this time, sodium ion and water follow so that isotonicity is maintained.
The major action of the toxin appears to be in the small intestine, although
it may also have some action in the colon. Interestingly enough, it has been
recently shown that a new gastrointestinal hormone vasoactive intestinal
peptide (VIP) which has a structure similar to secretin and glucagon appears
to act in exactly the same way as cholera toxin to stimulate adenyl cyclase,
eyclic AMP and active secretion of isotonic fluid. It has not yet been
demonstrated that cholera toxin releases VIP, however,

I think the problem with attempting to use cholera toxin for constipation
arises in the great difficulty that might SebeS in trying to properly control
the amount of active secretion that might be provoked. Constipation is usually
an idiopathic problem that can be readily handled by manipulating the diet and
giving osmotically active substances that will retain water within the intestinal
lumen. For many people, it is normal to have owly one or perhaps two bowel
movements per week; we do from time to time run into young adults who seem to
have bowel movements even less frequently. On the other hand, other people
normally have as many as three per day. I do have some opinions about con-
stipation in childhood, but have to admit that they are not firmly based on
scientific fact. I would be happy to chat with you about this sometime if you
wish.

Best regards.

Sincerely,

  

Gary M. Grfy, M.D.
Associate/Professor and Head
Division of Gastroenterology

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