Neurokinin NK1 receptors mediate plasma protein extravasation in guinea-pig dura

Selective neurokinin receptor agonists and calcitonin gene-related peptide (CGRP) were administered i.v. to anaesthetised guinea-pigs, and plasma protein extravasation was measured in dura and conjunctiva, intra- and extracranial tissues, respectively, innervated by the trigeminal nerve. The neurokinin NK1 receptor agonist, GR73632 enhanced plasma protein extravasation in guinea-pig dura (10 nmol/kg i.v.) and conjunctiva (3 and 10 nmol/kg i.v.). Pretreatment with the neurokinin NK1 receptor antagonist GR82334 (200 nmol/kg i.v.) blocked the response to GR73632 in both tissues. Neurokinin NK2 and NK3 receptor-selective agonists, GR64349 (10 nmol/kg i.v.) and senktide (30 nmol/kg i.v.) respectively, and also the neuropeptide CGRP (10 nmol/kg i.v.) had no significant effect on plasma protein extravasation in intra- or extracranial tissues. We conclude that the neurokinin NK1 receptor mediates plasma protein extravasation in tissues innervated by the trigeminal nerve in guinea-pigs; neurokinin NK2, NK3 and CGRP receptors do not directly mediate extravasation of plasma proteins in these tissues.