Pharmacological evidence for heterogeneity of ocular $aL₂ adrenoceptors

Abstract

Previous studies have shown that ocular $aL₂ adrenoceptors are located pre junctionally on sympathetic neurons and post junctionally on cells in the iris/ciliary body. While the activation of $aL₂ adrenoceptors at each site has been postulated to alter aqueous humor dynamics, little is known about the pharmacological characteristics of these receptors or their role in the modulation of anterior segment function. The purpose of the current study was to determine the possible heterogeneity of ocular $aL₂ adrenoceptors using relatively selective $aL₂ adrenoceptor agonists and antagonists to examine ocular pre- and post junctional $aL₂ adrenoceptors. Prejunctional $aL₂ effects were evaluated by means of the cat nictitating membrane (CNM) preparation. Postjunctional $aL₂ effects were evaluated by means of the cAMP assay in rabbit iris root/ciliary body. In the CNM, the administration of UK-14,304 (UK) produced a dose-related inhibition of neuronally mediated contractions. Pretreatment with the $aL₂ antagonist rauwolscine caused a 1 to 2 log unit right shift in the dose-response curve of UK in the CNM. However, pretreatment with $aL₂ antagonist SKF 104078 had no demonstrable effect on UK-induced inhibition of neuronally mediated contractions of the CNM. In the rabbit iris root/ciliary body, UK produced a concentration-dependent inhibition of cAMP accumulation on isoproterenol- and VIP-induced cAMP production. Pretreatment of iris root/ciliary bodies with SKF 104078 or rauwolscine reversed the inhibitory effect of UK on Isoproterenol- and VIP-induced accumulation of cAMP. These data provide the first evidence that the pre- and post junctional $aL₂ adrenoceptors represent pharmacologically distinct subpopulations of receptors in the eye. Moreover, these data indicate that drugs such as SKF 104078 can be used to determine the relative contributions of pre- and post junctional $aL₂ adrenoceptors in the modulation of aqueous humor dynamics.