Intraocular and cardiovascular effects of calcitonin gene-related peptide (CGRP)-I and -II in the rabbit.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide localized in the eye in the sensory nerves. In this study, the physiological effects of the two naturally occurring forms of human CGRP, CGRP-I, and -II, which differ only in three amino acids, have been demonstrated in the rabbit eye and cardiovascular system. Intravenously administered CGRP-I caused a biphasic increase in the intraocular pressure (IOP), disruption of the blood-aqueous barrier, and increase in the cyclic adenosine 3',5'-monophosphate (cAMP) content in the aqueous humor. CGRP-II caused a monophasic increase in the IOP and disruption of the blood-aqueous barrier, but no increase in the cAMP content occurred. CGRP-I and -II decreased the blood pressure in a similar dose-dependent manner. The effects of intracamerally administered CGRP-I and -II were very similar in the eye. An increase in the IOP, breakdown of the blood-aqueous barrier, and an increase in the cAMP content in the aqueous humor occurred. The differences in the biological responses between CGRP-I and -II in the rabbit eye might be a result of the different affinities of the CGRP forms to a single receptor. Alternatively, different subtypes of receptors for CGRP-I and -II may exist in the rabbit.