DIFFERENTIAL-EFFECTS OF 5-HT1B 1D RECEPTOR AGONISTS ON NEUROGENIC DURAL PLASMA EXTRAVASATION AND VASODILATION IN ANESTHETIZED RATS/

These studies compared the effects of the 5-HT1B/1D receptor agonists sumatriptan, CP-122 288 rolidinylmehtyl)-1H-indol-5-yl]methanesulphona mide succinate) and CP-93 129 5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]p yrid-5-one dihydrochloride) on neurogenic dural extravasation and vaso dilation in anaesthetized rats. Dural extravasation, evoked by high in tensity (1.2 mA) stimulation of the trigeminal ganglion, was measured using the radioactive plasma marker I-125-labelled bovine serum albumi n. Dural vasodilation produced by lower intensity (50-300 mu A) stimul ation of trigeminal fibres, was measured through a closed cranial wind ow using intravital microscopy. All compounds inhibited dural extravas ation (rank order of potency: CP-122 288 much greater than sumatriptan > CP-93 129) and dural vasodilation (rank order of potency: CP-93 129 much greater than sumatriptan = CP-122 288). Comparison of the potenc y of these compounds with their potencies in an in vitro functional mo del, agonist-induced [S-35]GTP gamma S binding, suggests that blockade of dural extravasation was consistent with an action at rat 5-HT1D re ceptors, 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-HT1B receptors. We suggest that in our preparations, production of dural vasodilation involves activa tion of trigeminal A delta-fibres whereas production of dural extravas ation involves activation of trigeminal C-fibres. The differential eff ects of compounds on dural extravasation and vasodilation may therefor e be due to the different receptor subtypes involved and to the select ive localization of these subtypes on different populations of trigemi nal sensory fibre. (C) 1997 Elsevier Science Ltd.