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Vasorelaxant and second messenger effects of maxadilan
S A Grevelink1, J Osborne, J Loscalzo
1Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown.
The Journal of Pharmacology and Experimental Therapeutics
|January 1, 1995
Summary
Maxadilan, a sand fly salivary protein, relaxes blood vessels by increasing cyclic AMP levels. Its potent vasodilatory effects are specific to certain vessel types, aiding blood acquisition.
Area of Science:
- Pharmacology
- Physiology
- Molecular Biology
Background:
- Maxadilan is a potent vasodilator derived from sand fly salivary gland extracts.
- Its primary known function is cutaneous vasodilation to facilitate blood meals.
Purpose of the Study:
- To investigate the vasodilatory mechanisms and vascular selectivity of maxadilan.
- To determine the cellular pathways involved in maxadilan's effects.
Main Methods:
- Testing recombinant and synthetic maxadilan on isolated rabbit aorta for relaxation.
- Assessing the impact of various receptor and channel blockers on maxadilan-induced relaxation.
- Measuring intracellular cyclic AMP levels following maxadilan treatment.
- Evaluating maxadilan's activity across different vascular beds (aorta, mesenteric artery, coronary arteries).
Main Results:
- Maxadilan induced endothelium-independent relaxations in rabbit aorta.
- Recombinant maxadilan (IC50 = 24 nM) was more potent than synthetic maxadilan (IC50 = 74 nM) in inhibiting norepinephrine-induced contractions.
- Blockers of common receptors and ion channels did not affect maxadilan's action.
- Maxadilan significantly increased cellular cyclic AMP levels (2-3 fold).
- Activity was highest in rabbit aorta and mesenteric arteries, with no effect on coronary arteries.
Conclusions:
- Maxadilan acts via a novel mechanism, likely by elevating intracellular cyclic AMP in smooth muscle cells.
- Its vasodilatory effects are selective for specific blood vessels.
- This mechanism contributes to the sand fly's ability to obtain a blood meal.