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BRIEF PROPOSAL MAST CELLS AND MIGRAINES THEOHARIS CONSTANTIN THEOHARIDES* The mast cell, tissue basophil, or wandering histiocyte—as it is often called—is primarily known for its involvement in allergic disease states [1, 2]. Although described by Paul Ehrlich more than 100 years ago [3], it has persistendy evaded most attempts to uncover its physiological function [4, 5]. More recendy, the mast cell has become die target of new speculation aspiring to endow it with certain physiological attributes [6]. Clearly, the interest lies in the great variety of biologically active molecules which are stored in mast cell granules and which can be released, along with other molecules produced during the release reaction, with appropriate stimulation [7, 8]. Aldiough allergic secretion from mast cells involves a rather explosive release of all of its known secretory products, and probably a whole lot more, very little is known about the type of secretion that may be going on physiologically. Possible mechanisms for such "physiologic" secretion may be related to the findings that mast cells are able to secrete the content ofonly a few of their granules [9], and possibly certain of dieir secretory products differentially [10]. Given these findings, it seems attractive to propose that differential or sequential release of certain vasoactive molecules from mast cells may participate in die pathophysiology of migraines. Migraines, or hemikranies (the Greek term from which the English one is derived ), may be briefly described as recurrent attacks ofheadaches which can vary in duration, frequency, and intensity. Migraines are often unilateral, are associated with stress, tend to be familial, and are sometimes dubbed as psychosomatic; their etiology remains unknown. Although diere have been a number of recent reviews [11, 12] and hypotheses [13, 14] on migraines, there is no particular consensus odier than the indicated involvement of vasoactive and pain-inducing molecules such as serotonin and substance P. Naturally, a single responsible compound, tentatively called "neurokinin," has also been proposed and is being sought. Current dogma has it that migraines are composed of two phases: first, there is a vasoconstriction of certain vessels, soon followed by their dilatation and the intense feeling ofa throbbing, pulsating, and often unbearable headache. It appears that the carotid arteries, of which the external is particu- * 4281 Yale Station, New Haven, Connecticut 06520. Permission to reprint this brief proposal may be obtained only from the author. 672 I Theoharis Constantin Theoharides · BriefProposal larly well supplied widi sensory nerve endings, may be specifically involved [11, 12]· Mast cells are ubiquitous in all organs ofthe body and are particularly plentiful around vessels [1,2]; certain types of mast cells line up the microvasculature of die central nervous system [15, 16] and appear to be involved in cerebral vasospasm [17]. It is therefore apparent that mast cells occupy a particularly appropriate position for participation in die control of vasculature which may be involved in migraines; these latter mast cells have not been studied in detail. In general, however, mast cells can secrete serotonin and Ieukotrienes, which are potent smooth-muscle constrictors, as well as histamine and substance P, which are powerful vasodilators [6, 7, 18]. Mast cells also secrete a variety of enzymes which could lead to die production of other vasoactive and especially painproducing molecules [6], such as those of the kinin family. Indeed, it was recently shown diat mast cells can secrete kallikrein-like enzymes which catalyze the synthesis ofkinins [19, 20], molecules which are particularly active in eliciting pain [21, 22]. Moreover, preliminary evidence indicates that at least in one instance , kallikrein-like activity may be secreted differentially [23]. After possibly satisfying the requirements for a cell type, the location and secretory products of which may allow it to participate in the pathogenesis of migraines, the critical factor left to be addressed is time. Here, again, the mast cell may fulfill the criteria for a sequential secretion of vasoconstrictor, followed by vasodilator and pain-producing substances. For instance, under certain conditions , the mast cell has been shown to release serotonin in the absence of histamine and without any obvious degranulation [10, 24]; this type of release appears to involve specific serotonin-binding proteins [25]. It is therefore reasonable to expect mat serotonin or...

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Additional Information

ISSN
1529-8795
Print ISSN
0031-5982
Pages
pp. 672-675
Launched on MUSE
2015-01-07
Open Access
No
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