[Increase in beta-adrenergic receptors in rabbits in long-term local administration of beta-blockers]

Chronic application of beta-blockers often induces tachyphylaxia of unknown origin. After long-term topical pretreatment of pindolol and timolol in rabbit eyes (up to 12 weeks, twice a day) beta 2-adrenergic receptors were localized and quantified with autoradiographic methods. Frozen sections of albino rabbit eyes were labelled with [125I] cyanopindolol. Quantification revealed a significant increase in the density of beta 2-receptors after premedication with pindolol in the ciliary body and the corneal epithelium. This increase was detectable after 2 weeks of premedication and reached its maximum after 4 weeks. After premedication with timolol a significant increase of beta 2-receptors in the epithelium of the ciliary body and the corneal epithelium was visible. Following pindolol over an equivalent time-course, to that of timolol administrations, an increasing number of beta 2-receptor sites was also observed. No significant changes were visible for either kind of premedication investigated (pindolol/timolol) in the corneal endothelium, the lens or the choroid. Chronic application of topically instilled beta-blocking agents leads to a significant increase in receptor density in ocular structures that are involved in aqueous humor production. This up-regulation of beta 2-adrenergic receptors might explain the intraocular events at receptor level in relation to the phenomenon of tachyphylaxis.