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Pituitary adenylate cyclase-activating polypeptide (PACAP) is one of the nine hormones in the PACAP/glucagon superfamily of hormones. Scientists believe it is the ancestral molecule of the superfamily, because it has remained 96 percent unchanged for 700 million years. This long evolutionary conservation also indicates that it is likely essential for survival in animals that produce it. PACAP is found in the muscular, cardiovascular, nervous, endocrine and immune systems of the body, and seems to be essential for the proliferation, differentiation and apoptosis of many cell types. As of mid-2011, scientists were still searching for the physiological trigger for PACAP release and working to learn more details about the hormone's many functions.
Scientists first discovered this hormone in 1989. As of mid-2011, researchers had identified it in six vertebrate species, including humans, other mammals and some species of reptiles, fish and amphibians. PACAP also was present in at least one ancient species, a protochordate called the tunicate. Tunicates lived 700 million years ago, and the nucleotides that make up tunicate PACAP have only a 4 percent difference in complementary deoxyribonucleic acid (cDNA) compared to those in human PACAP. This tremendous level of conservation leads scientists to believe the molecule is a key to the survival of any species that contains it.
In humans, PACAP is found in the cardiovascular, muscular, nervous, endocrine and immune systems. It plays a key role in the metabolism of proteins and carbohydrates, which makes it essential for life. It also seems to be involved in regulating the function of smooth and cardiac muscle; endocrine, paracrine and exocrine excretions; and immune response. Variation of a gene that regulates PACAP production may play a role in post-traumatic stress disorder in females. As of mid-2011, scientists had identified several types of receptors for PACAP but were still struggling to identify the specific physiologic trigger for its release.
In addition to its roles in metabolism and other body functions, PACAP seems to be important for normal development in humans, especially development of the nervous system. The hormone regulates cell division and proliferation in several types of cells throughout the nervous system and in smooth muscle. It also seems to be involved in the regulation of cell differentiation in the nervous and reproductive systems, and in apoptosis of nervous system cells. The molecule also may be involved in the development of the pancreas, liver, retinas and adrenal gland. Many types of cancerous tumors contain PACAP, which is thought to play a role in the growth and development of the tumors.
Continued research into the hormone's function is expected to help scientists better understand the physiology and development of the human body. Such study also may facilitate research into PACAP-containing cancers, such as neuroblastoma and cancers of the pancreas and prostate. A better understanding of its roles in cardiovascular function, such as its role as a relaxant of smooth muscle in the aorta, may help physicians treat disorders of the cardiovascular system. Researchers continue to conduct human and animal studies in an effort to achieve these goals.