Effects of intravenous calcitonin gene-related peptide (CGRP) and substance P on the blood-aqueous barrier in the rabbit.
The irritation response of the rabbit eye to trigeminal nerve stimulation, which includes a breakdown of the blood-aqueous barrier (BAB), seems to be due to the release of substance P (SP) and calcitonin gene-related peptide (CGRP). In order to assess the relative importance of these two peptides for the barrier effect, and the role of arachidonic acid metabolites (AAM) in the response, we have studied the effects of intravenous injections of the peptides on the permeability of the blood vessels of the anterior uvea and the BAB using labelled albumins. At a dose of 120 pmol kg-1 there was marked leakage of labelled albumin into the aqueous humour in animals under pentobarbital anaesthesia. The leakage was enhanced by sympathotomy. In conscious animals 5 pmol kg-1 CGRP caused enhanced leakage from the blood vessels of the ciliary processes in those pre-treated with biperiden in order to abolish the cholinergic vasoconstrictor tone in the anterior uvea. 24 and 120 pmol kg-1 CGRP caused marked leakage of albumin and a breakdown of the epithelial part of the BAB. These effects were not modified by biperiden pre-treatment, but markedly reduced by pre-treatment with indomethacin. The protecting effect of indomethacin was lost when biperiden was given as well. SP did not cause a leakage with 5 nmol kg-1 and only moderate leakage with 25 nmol kg-1. This effect was abolished by pre-treatment with indomethacin but not if indomethacin was combined with biperiden.(ABSTRACT TRUNCATED AT 250 WORDS)
Andersson
S E
SE
Department of Physiology and Medical Biophysics, University of Uppsala, Sweden.
Bill
A
A
D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide; D002199:Capillary Permeability / Q000187:drug effects*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage*; D011817:Rabbits; D013373:Substance P / Q000008:administration & dosage*; D014602:Uvea / Q000187:drug effects*
D009479:Neuropeptides; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin