Vasoactive intestinal polypeptide (VIP) was originally isolated from the small intestine and the lung as a peptide with potent vasodilator effects (Said and Mutt 1970) and has recently been suggested to play a major regulatory role in a large number of acute and chronic diseases (Delgado, Abad, Martinez, Leceta, and Gomariz 2001; Delgado and Ganea 2001). The name VIP is derived from the profound and long-lasting gastrointestinal smooth muscle relaxation that this peptide produces following systemic administration. The primary structure of VIP is closely related to pituitary adenylate cyclase activating polypeptide (PACAP). VIP contains 28 amino acid residues with a molecular weight of 3326 Da. The amino acid sequence of VIP in the rat, human and other mammalians species is identical (Henning and Sawmiller 2001).

VIP has recently been attributed to function not only as a vasodilator and bronchodilator but also as a potent immunomodulator. VIP is a critical mediator of neuronal development and survival, hormone secretion, smooth muscle function, glandular secretion, cellular migration, adhesion and production of cytokines, and other proteins. VIP also regulates negatively and positively the generation of cytokines by macrophages and lymphocytes (Said and Mutt 1988). Furthermore, several studies indicated that VIP has a significant role in sleep regulation.

On the other hand, prolactin (PRL) is a hormone expressed in mammals, birds, reptiles, amphibians, and fishes, and has a wide spectrum of effects. In fact, more than 300 distinct biological activities of PRL have been recorded (Nicoll 1980). PRL is expressed in many extrapiuitary sites, particularly within the female and male reproductive organs (uterus, mammary gland, prostate), cells of the immune system (T cells, B cells, NK cells), and certain brain regions, acting locally as an autocrine or paracrine cytokine in diverse tissues and cells. It is produced by lactotrophs and somatolactotrophs of the anterior pituitary. PRL has a wide range of cellular and physiological effects. The effects are cell and context dependent.

The regulatory neuropeptide VIP, and cytokines such as PRL, are multifunctional pleiotropic proteins that play crucial roles in cell-to-cell communication and cellular activation. Both molecules are involved not only in the immune response but also in a variety of physiological and pathological process, including the sleep regulation.

In the present chapter we describe the biological activities of VIP and PRL on the central nervous system (CNS), with special emphasis on role they have on sleep and some immune system regulations.

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