vasoactive-intestinal-peptide and Erythema

Neurokinins are a family of peptides which are released from sensory nerves. This family involves substance P, neurokinin A and B which stimulate neurokinin-NK1, -NK2 and -NK3 receptors respectively. The neurokinins as well as C.G.R.P. (calcitonin gene related peptide) and V.I.P. (vasoactive intestinal peptide) are the mediators of the non adrenergic non cholinergic (N.A.N.C.) nervous system. All these peptides can be released by nerve fibres innervating the skin. They are mainly inflammatory mediators. At skin level, the neurokinin induce itch, wheal and flare. Itch and flare are partly due to histamine release from mast cells in response to substance P.

Topics: Amino Acid Sequence; Animals; Calcitonin Gene-Related Peptide; Edema; Erythema; Histamine Release; Humans; Mast Cells; Molecular Sequence Data; Neurons, Afferent; Pruritus; Receptors, Tachykinin; Skin; Skin Diseases; Tachykinins; Vasoactive Intestinal Peptide

Gut peptide secreting tumours originate most commonly from the pancreatic Islets of Langerhans. Tumours at a variety of other sites have also been shown to synthesize and release these peptides, reflecting the wide distribution of the peptide secreting cells of the diffuse neuroendocrine system. Tumours such as the glucagonomas, insulinomas, VIPomas and gastrinomas are associated with characteristic clinical syndromes resulting from the effects of the peptide they secrete. The majority of the islet cell tumours in fact secrete a number of different peptides and many of these are present in several molecular forms, some of which may not be biologically active. This may explain the lack of clinical sequelae in association with tumours such as the somatostatinomas. The clinical features, methods of diagnosis, localisation and treatment of these tumours will be discussed.

Topics: Adenoma, Islet Cell; Bombesin; Bronchial Neoplasms; C-Peptide; Carcinoma, Small Cell; Diagnosis, Differential; Endocrine System Diseases; Erythema; Gastrointestinal Hormones; Glucagon; Glucagonoma; Humans; Insulin; Insulin Secretion; Insulinoma; Male; Neoplasms; Neurotensin; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatic Polypeptide; Somatostatinoma; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Responses to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) were investigated in atopic eczema (AE) patients. To elucidate the involvement of histamine to ACh-provoked vasoreactions and sensations, we applied a selective H1-antagonist (cetirizine) 3 h prior to the ACh-administration. Solutions of acetylcholine (ACh, 0.55 M) and vasoactive intestinal polypeptide (VIP, 1.5x 10(-5) M) were injected (10 microl) intracutaneously into the volar forearm of 14 healthy subjects and 14 atopic eczema (AE) patients. The substances were applied as single stimulus as well as in combination. Sensations evoked by the stimulation were recorded using 2 visual analog scales (VAS). Vasoreactions were analyzed with the new technique of computer assisted video image analysis. With this method we measured the dynamics of the flare development and the extension of the final flare size independent of the observer's assessment. In control subjects the development and extension of the final flare size was almost similar, regardless whether ACh and VIP were applied in combination or separately. Compared to healthy controls, after injection of ACh, VIP and the combination of VIP and ACh smaller flare sizes were recorded in AE patients. After VIP was given, the control subjects reported pruritus, which was significantly augmented compared to AE patients. In contrast, controls reported a burning pain after the injection of ACh, whereas AE patients felt predominantly pruritus. Itch sensation after the combined application of VIP and ACh was significantly elevated in AE patients. Consequently, we assume that mediators of sudomotor neurons, i.e., VIP and ACh meet in AE patients apparently sensitized nociceptive primary afferents and induce exaggerated itch, pain and flare responses. When pretreated with the selective H1-antagonist cetirizine before ACh was injected, pain and erythema due to ACh was diminished in healthy controls. In contrast, cetirizine did not influence the size of erythema and the magnitude of sensation in AE patients. We conclude, that the release of histamine is not involved in ACh-induced erythema and pruritus in AE. These data provide evidence that pruritus can be elicited in atopic eczema by a cholinergic, histamine independent mechanism.

Topics: Acetylcholine; Adult; Cetirizine; Cholinergic Agents; Cross-Over Studies; Dermatitis, Atopic; Double-Blind Method; Erythema; Female; Histamine H1 Antagonists; Humans; Injections, Intradermal; Male; Pain; Pruritus; Psychophysics; Skin; Vasoactive Intestinal Peptide