Physiology and Pharmacology of C-fibres in the rabbit eye

Abstract: C-fibre neuropeptides, such as tachykinins and calcitonin-gene related peptide (CGRP), play an important role in neurogenic inflammation. The present work deals with five different aspects of the physiology and pharmacology of C-fibres. 1) Tachykinin receptor antagonists of peptide and non-peptide nature have been employed to identify the tachykinin receptors of the rabbit iris as NK1 and NK3 types. 2) The mode of action of capsaicin, resiniferatoxin, bradykinin and capsaicin antagonists in the rabbit iris has been examined. The results suggest the existence of C-fibre subtypes and/or capsaicin receptor subtypes. 3) Pituitary adenylate cyclase-activating peptide (PACAP) is a novel C-fibre neuropeptide. The PACAP-induced ocular effects mimicked the symptoms of inflammation and the PACAP concentration in the aqueous humor was increased greatly following noxious stimulation, indicating that the peptide contributes to ocular inflammation. Also, PACAP seems to activate C-fibres. 4) The actions of nitric oxide (NO) have been ascertained in three ocular inflammatory models. NO was found to be involved in the activation of C-fibres and to mediate some of the ocular effects of CGRP and PACAP. The results suggest that NO plays an important role in the ocular inflammation. 5) mRNA coding for preprotachykinin-A (PPT-A) was demonstrated in the rabbit iris. It is released into the aqueous humor following noxious stimulation. Our results suggest that the PPT-A mRNA occurs in C-fibres and that it is released in response to stimulation.