Effects of aging on prejunctional control of neurotransmission in the rat.
In this study, we have looked in detail at the effects of aging on neurotransmission in isolated atria and intact heart in anesthetized rats, examining adult and aged animals. There was a diminished ability of the norepinephrine reuptake blocker cocaine to increase stimulation-evoked release of norepinephrine in aged rats and in terms of increasing the norepinephrine-evoked tachycardia in anesthetized rats, suggesting that the function of the reuptake process is diminished by aging. The ability of the alpha 2 adrenergic receptor agonist xylazine to inhibit release of norepinephrine neurotransmitter was also diminished in aged rats both in isolated tissues and in vivo in anesthetized animals. In further studies, the ability of the beta-adrenergic receptor agonists isoproterenol (beta 1 and beta 2 agonist) and procaterol (selective beta 2 agonist) to increase stimulation-evoked release of norepinephrine was examined. Both agonists produced a concentration-dependent facilitation of norepinephrine release in rats atria. Although isoproterenol and procaterol increased release in tissues from young and old animals, the magnitude of the increase was significantly reduced in tissues from old rats, so that beta-adrenergic receptor mediated facilitation was diminished. In summary, aging is associated with a decline in prejunctional modulation of neurotransmission, in terms of diminished norepinephrine reuptake, diminished prejunctional alpha 2 adrenergic receptor mediated inhibition and diminished prejunctional beta 2 adrenergic receptor mediated facilitation. TABLE 2 summarizes the possible effects of aging on noradrenergic neurotransmission. Overall, neurotransmission at rest may be little changed by aging, given that postjunctional responsiveness may fall, but scope for modulation may be diminished.
Docherty
J R
JR
Department of Physiology, Royal College of Surgeons, Dublin, Ireland.
D000320:Adrenergic Fibers / Q000502:physiology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D014649:Vas Deferens / Q000187:drug effects; D014991:Xylazine / Q000494:pharmacology
D002395:Catecholamines; D018377:Neurotransmitter Agents; D014991:Xylazine; D003000:Clonidine