학술논문
Differential Effects of 5-HT1B/1DReceptor Agonists on Neurogenic Dural Plasma Extravasation and Vasodilation in Anaesthetized Rats
Document Type
Article
Source
Neuropharmacology; April-May 1997, Vol. 36 Issue: 4-5 p525-533, 9p
Subject
Language
ISSN
00283908
Abstract
These studies compared the effects of the 5-HT1B/1Dreceptor agonists sumatriptan, CP-122 288 ((R)-N-methyl-[3-(1-methyl-2-pyrrolidinylmethyl)-1H-indol-5-yl]methanesulphonamide succinate) and CP-93 129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one dihydrochloride) on neurogenic dural extravasation and vasodilation in anaesthetized rats. Dural extravasation, evoked by high intensity (1.2 mA) stimulation of the trigeminal ganglion, was measured using the radioactive plasma marker 125I-labelled bovine serum albumin. Dural vasodilation produced by lower intensity (50–300 μA) stimulation of trigeminal fibres, was measured through a closed cranial window using intravital microscopy. All compounds inhibited dural extravasation (rank order of potency: CP-122 288 ⪢ sumatriptan > CP-93 129) and dural vasodilation (rank order of potency: CP-93 129 ⪢ sumatriptan = CP-122 288). Comparison of the potency of these compounds with their potencies in an in vitrofunctional model, agonist-induced [35S]GTPγS binding, suggests that blockade of dural extravasation was consistent with an action at rat 5-HT1Dreceptors, but activity at another, unknown, “extravasation receptor” could also be involved. In contrast, inhibition of dural vasodilation was consistent with an action at rat 5-HT1Breceptors. We suggest that in our preparations, production of dural vasodilation involves activation of trigeminal Aδ-fibres whereas production of dural extravasation involves activation of trigeminal C-fibres. The differential effects of compounds on dural extravasation and vasodilation may therefore be due to the different receptor subtypes involved and to the selective localization of these subtypes on different populations of trigeminal sensory fibre. © 1997 Elsevier Science Ltd.