5-CARBOXAMIDO-TRYPTAMINE, CP-122,288 AND DIHYDROERGOTAMINE BUT NOT SUMATRIPTAN, CP-93,129, AND SEROTONIN-5-O-CARBOXYMETHYL-GLYCYL-TYROSINAMIDE BLOCK DURAL PLASMA-PROTEIN EXTRAVASATION IN KNOCKOUT MICE THAT LACK 5-HYDROXYTRYPTAMINE(1B) RECEPTORS

We studied the dural plasma protein extravasation response after unila teral electrical stimulation of the trigeminal ganglion in mice lackin g serotonin 5-HT1B (5-HT1D beta) receptors by modifying a technique pr eviously described in rats or guinea pigs. We investigated the inhibit ory effects of six 5-HT1 receptor agonists in this model: 5,6-tetrahyd ropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP-93,129), sumatriptan, serot onin-5-O-carboxymethylglycyl-tyrosinamide (GTI), ethyl-3-(N-methylpyrr olidin-2R-ylmethyl)-1H-indole (CP-122,288), 5-carboxamido-tryptamine ( 5-CT), and dihydroergotamine. The plasma extravasation response did no t differ between wild-type and mutant after vehicle injection. The pot ency of sumatriptan, CP-122,288, CP-93,129, and 5-CT in wild-type mice was similar to that previously reported for rats. CP-122,288 (1 nmol kg), 5-CT (1 nmol/kg), and dihydroergotamine (72 nmol/kg) inhibited pl asma protein extravasation within dura mater after electrical trigemin al ganglion stimulation in both wild-type and knockout mice, which sug gests that these agonists act predominantly via receptors other than 5 -HT1B. Unlike in wild-type mice, CP-93,129 (1.4 mu mol/kg), a specific 5-HT1B receptor agonist, had no effect in knockout mice. The same hel d true for sumatriptan (0.7 mu mol/kg) and GTI (0.6 mu mol/kg). These results suggest that CP-93,129, sumatriptan, and GTI exert their effec ts via 5-HT1B (5-HT1D beta) receptors in mice.