Denervation supersensitivity and beta-adrenergic receptors as a function of age

The density and ontogenetic development of beta-adrenergic receptors varies in the different brain areas. The density of receptors in pineal gland, which at maturity is the highest of the brain areas studied, increases rapidly soon after birth, whereas the density of beta-receptors in cerebellum does not increase from birth. This development of beta-receptors in pineal gland is temporally related to the development of the sensitivity of adenylate cyclase to norepinephrine. Preventing the sympathetic innervation to the pineal gland before it has ever been innervated does not impede development of beta-adrenergic receptors. That is, the beta-receptors can develop in the absence of sympathetic input to the gland. In fact, reducing sympathetic input, particularly after the receptors have developed, causes an increase in the number of beta-adrenergic receptors and a concomitant increase in the response of adenylate cyclase to norepinephrine. With advanced age the number of beta-adrenergic receptors declines in several areas of the brain. This reduction may explain the reduced ability of aged tissue to respond to adrenergic agonists. The mechanism for this decrease in beta-adrenergic receptors with age may be related to a reduced ability of aged tissues to produce compensatory increases in their receptor density in the face of decreased sympathetic input.