Pharmacological Sciences

Biology of VIP and Related Neurotransmitters; Mediation and
Modulation of Lung Injury and Bronchial Asthma

Sami I.
Said, M.D.
Professor : Medicine and Physiology M.D.,
University of Cairo

My work with VIP (vasoactive intestinal peptide) began with
its discovery, first in the lung and intestine, then in the brain and
nerve cells. Research on VIP and related peptides has taken me and
my colleagues on an exciting journey through many organ systems and across
different disciplines, including physiology, pharmacology, biochemistry,
endocrinology, and neuroscience. One of our objectives is to define the
physiological role of these peptides, their relationship to disease, and their
therapeutic potential. Our approaches include the use of cells in culture,
tissue strips, isolated organ preparations, anesthetized animals, and clinical
trials in human subjects.

Our major research focus is on cell injury and inflammation,
the principal processes underlying the adult respiratory distress syndrome and
bronchial asthma, both common disorders and major health problems. Our
aim is to analyze the basic mechanisms by which cell and tissue injury occurs,
and to identify pharmacological means of guarding against the injury, both in
animal models and in clinical practice.

In addition to peptides that are structurally related to VIP,
such as helodermin and pituitary adenylate cyclase-activating peptide (PACAP),
the recently recognized transmitter nitric oxide (NO) is a target of our investigations.
Under physiological conditions, NO and VIP work, via different signal transduction
pathways, to promote smooth muscle relaxation and other functions. In
the setting of tissue injury and inflammation, however, they play opposing
roles, with NO acting as mediator and VIP as modulator.

Selected Publications

• Said, S.I., ed. (1991). "The Pulmonary Circulation and Acute Lung Injury",
  2nd Ed., Futura, Mount Kisco, New York, 590 pp.
• Pakbaz, H., Foda, H.D., Berisha, H.I., Trotz, M., and Said, S.I. (1993).
  Paraquat-induced lung injury: Prevention by vasoactive intestinal peptide
  (VIP) and the related peptide helodermin. Am. J. Physiol. 265 (Lung Cell. Mol. Physiol. 9): L369-L373.
• Berisha, H.I., Pakbaz, H., Absood, A., and Said, S.I. (1994). Nitric
  Oxide as a mediator of oxidant lung injury due to paraquat. Proc.
  Natl. Acad. Sci. USA 91: 7445-7449.
• Said, S.I., Berisha, H.I., and Pakbaz, H. (1995). NMDA receptors outside
  the CNS: activation causes acute lung injury that is mediated by nitric
  oxide synthesis and prevented by VIP. Neuroscience 65:
  943-946.