Circadian variations of adrenergic receptors in the mammalian pineal gland: A review

Abstract

Pineal adrenergic receptor numbers show circadian variations in both rat and Syrian hamster. In the rat pineal beta-adrenergic receptor density reaches peak values either late in the light phase or at middark; the differences in the circadian phase seem related to the light:dark cycle to which the animals are exposed. No circadian rhythm of pineal alpha-adrenergic receptors is documented in intact rats. In the Syrian hamster pineal beta-adrenergic receptor density is high throughout the light phase and drops to minimal values at the time of the nocturnal peak of melatonin production. The circadian rhythm of pineal alpha-adrenergic receptor numbers runs parallel to the beta-adrenergic receptor variation, but is less pronounced. In the rat, pineal melatonin production is rapidly induced by beta-adrenergic agonists at any time during a 24-hour period, even when the pinealocyte beta-adrenergic receptor number is lowest (early in the light phase). In contrast, the Syrian hamster pineal seems most responsive to beta-adrenergic agonists in the late night while being less responsive during the day when beta-adrenergic receptor density is high. Interestingly, the human pineal gland is also not especially responsive to adrenergic stimulation during the light phase, possibly making the Syrian hamster pineal a better model than the rat pineal for determining neural/pineal interactions in humans. Comparison of the circadian variations in pineal adrenergic receptors leads to the conclusion that the functional differences between rat and hamster pineal are probably not explicable in terms of the adrenergic receptors, but are caused most likely by (a) intracellular mechanism(s) beyond the adrenergic receptors.

Diurnal variation of the adenylyl cyclase type 1 in the rat pineal gland.

“…This is in apparent contradiction with the fact that the amount of ,B-adrenergic receptors in the pineal gland has been reported to follow a circadian pattern (31). However, the amplitude of the variation is small (less than 50% of peak-through-mean) (37). Indeed, as shown by Post et al (38), the number of AC molecules is actually the main limiting step in the receptor/ Gsa/effector cascade.…”

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

“…3. Other cellular mechanisms: ␤ 1 -AR are desensitized toward the end of the night (Pangerl et al, 1990;Freedman et al, 1995); a feedback effect of PKC on the ␣ 1 -AR-induced increase in Ca 2ϩ i occurs ; specific phosphatases may inhibit NE-induced cyclic nucleotide production and CREB phosphorylation ; the size of the Aa-nat transcript decreases at night, reflecting a reduction in the polyadenylated tail, a mechanism known to decrease transcript stability and translation efficiency ; a decrease in AA-NAT activity could also result from a mechanism of protein thiol:disulfide interaction (Namboodiri et al, 1981); S-adenosyl-L-homocysteine, which accumulates during the night, may inhibit HIOMT activity (Tedesco et al, 1994); and finally, reduced MEL synthesis could result from a decrease in the quantity of its substrates.…”

The effect of feed restriction and of a β-adrenergic agonist on plasma melatonin concentrations in domestic pigs

“…Data from other species indicate that the nocturnal production of melatonin is principally the result of the refuase of norepinephrine from the sympathetic neurons terminating in the pineal (Pangerl et al 1990). Norepinephrine intericts with c-and B-adrenergic receptors on the membranes of the pinealocytes, leading to an increase in intracellular cyclic adenosine monophospate, which, in turn, mediates an increase in NAT, the rate-limiting enzyme in melatonin production.…”