Current Pharmaceutical Design - Volume 7, Issue 2, 2001

Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad distribution in the body that exerts very important pleiotropic functions in several systems. The present work reviews the immunology of VIP. Being daring, this neuropeptide could be included in the group of cytokines since it is produced and secreted by different immunocompetent cells in response to various immune signals, plays a broad spectrum of immunological functions, and exerts them, in a paracrine and/orautocrine way, through three different specific receptors. Although VIP has been classically considered as an immunodepressant agent, and its main described role has been as an anti-inflammatory factor, several evidences suggest that a better way to see this peptide is as a modulator of the homeostasis of the immune system. In the last decade, the pharmacology of VIP has spectacularly grown, and VIP itself, as well as more stable VIP-derived agents, have been used or proposed as efficient therapeutical treatments of several disorders, specially inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis, Crohn´s disease and autoimmune diabetes. A broad field of perspectives is actually open, and further investigations will help us to definitively understand the immunology of this ”very important peptide“

Nerve growth factor (NGF) is known to be essential for the survival of peripheral and brain neurons, and according to more recent studies alsofor a variety of cells localized in the immune system. Basic and preclinical findings published in the last 15-20 years have prospected the hypothesis that NGF can be pharmaceutically useful for promoting healing in certain peripheral and central neurological insults. We have recently provided evidence that NGF applied topically, has a therapeutic potentiality for human corneal and pressure ulcers, and more recently in vasculitis induced by rheumatoid arthritis. This review will summarize previous and ongoing evidence supporting the role of NGF in the nervous and immune system and discuss NGF potentiality as a pharmacological tool for basic and clinical studies.

Leptin has emerged as a major regulator of adiposity. Leptin is released into the blood from fat cells and circulates to the brain where it crosses the blood-brain barrier (BBB) to act at receptors within the central nervous system to affect appetite, thermogenesis, and a number of other actions. In humans and in many rodent models, resistance to leptin appears to be a chief cause of obesity. Determining the cause of leptin resistance is fundamental to developing strategies for the use of leptin in obesity. The literature characterizing the transport of leptin across the BBB is reviewed. This literature strongly suggests that the cause of leptin resistance is due a decreased transport of leptin across the BBB in obese humans and rodents. The main cause of this resistance appears to be an impairment in the activity of the transporter rather than just simply saturation at higher doses. Strategies to overcome impaired BBB transport are reviewed, including the use of allosteric regulators and the delivery of material by the intrathecal route.

Plasma kinins are a family of peptides which play an important role in a variety of pathophysiological conditions. As a consequence of the progress in the area of kinin receptors, specific kinin receptor antagonists will be available in near future in order to provide more selective therapeutic modalities for the treatment of diseases such as asthma, cardiovascular diseases, inflammation, pain, etc.Although the initial observation leading to dicovery of kinins has been performed in 1909, important progress on the development of specific kinin receptor antagonists has been made in last two decades. This review emphesizes the physiological functions of kinins along with their receptor subtypes and post-receptor events in the cellular signaling. In this article, the latest developments in the kinin receptor antagonists including nonpeptide ones have been reviewed