[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.
Kahle
G
G
Universitäts-Augenklinik Rudolf Virchow, Berlin.
Kaulen
P
P
Scherer
V
V
Wollensak
J
J
D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D002924:Ciliary Body / Q000187:drug effects* / Q000473:pathology; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D008134:Long-Term Care; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000648:ultrastructure; D013999:Timolol / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D018343:Receptors, Adrenergic, beta-2; C047975:cyanopindolol; D013999:Timolol; D010869:Pindolol
Zunahme von beta-adrenergen Rezeptoren bei Kaninchen unter lokaler Langzeitapplikation von beta-Blockern.