Anin vivomodel for dissociating α2- and DA2-adrenoceptor activity in an ocular adnexa: Utility of the cat nictitating membrane preparation

Abstract

Recent reports from this laboratory indicate that dopamine (DA₂) agonists can lower intraocular pressure (IOP) in rabbits, monkeys and rats. This communication suggests that the cat nictitating membrane (CNM) preparation is a useful model for localizing the site(s) and mechanism(s) of action of dopamine (DA₂) agonists and that this model can be used to discriminate between ot₂ and DA₂ activity. This in vivo preparation consists of indirect (neuronal)- and direct (agonist)-induced activation of the CNM by: 1) pre-and postganglionic stimulation of sympathetic nerves and 2) injection of norepinephrine (NEPI) into the external carotid artery (i.a.). A variety of DA₂-agonists (ergolines, azepines, aminotetralins, aporphines) can cause dose-dependent depression of neuronally mediated contractions with minimal effects on contractions elicited by NEPI i.a. Characteristically, DA₂-agonists depressed contractions elicited by low frequency (2 & 4 Hz) stimulation more than high frequency (6 & 8 Hz) stimulation. For example, the inhibitory effects of an ergoline derivative LY141865 on neuronally mediated contractions of the CNM could be reversed (or prevented) by relatively selective DA₂ antagonists, such as sulpiride and domperidor.e, but not by relatively selective α₂-antagonists, such as yohimbine and rauwolscine. Interestingly, a₂-adrenoceptor agonists, such as clonidine and xylazine, caused less depression of nerve-stimulated responses than did DA₂-agonists at the same dose. This modest suppression by o₂-agonists could be inhibited by yohimbine but not by sulpiride or domperidone. These results with the CNM document the. presence of DA₂ receptors on sympathetic neurons innervating an ocular adnexa and demonstrate a model for dissociating DA₂ from α₂activity.