Response and level of beta-adrenergic, vasoactive intestinal peptide, and PACAP receptors during the circadian cycle

To determine whether a nocturnal increase of ciliary process beta-adrenergic receptor responsiveness can explain the observation that timolol decreased the aqueous flow rate and intraocular pressure (IOP) during the night but not during the day in rabbits.

Rabbits were housed in alternating 12-hour periods of light and dark. In vitro stimulation of tissue cyclic adenosine monophosphate (cAMP) levels by isoproterenol (ISO), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), or a soluble derivative of forskolin (sFSK) was measured in ciliary processes harvested at mid-light phase and early and late dark phase. Inhibition of ISO and VIP stimulation of ciliary process cAMP by an alpha 2-adrenergic agonist and maximal binding of [125I]I-pindolol, [125I]I-VIP, and [125I]I-PACAP in ciliary process membranes were measured at the same three times.

Although there may have been a nocturnal increase in the sensitivity of ciliary process cAMP levels to stimulation by ISO, this was not observed consistently, VIP, but not PACAP, stimulation increased at night, but there was no change in the response to sFSK. Inhibition by apraclonidine of elevated ciliary process cAMP levels was constant at all three times. Ligand-binding studies showed little change in ciliary process beta-adrenergic, VIP-, or PACAP-receptor levels at the three times.

There is no convincing evidence for a nocturnal increase in beta-adrenergic receptor sensitivity in rabbit ciliary processes that could explain the difference between day and night effects of timolol on aqueous flow and IOP.