Effects of aging on mechanisms of alpha-adrenergic and dopaminergic action.

Mammalian parotid glands have provided excellent model systems for studying adrenergic control of defined biochemical and physiological processes during exocrine secretion. The findings point to a deficiency in a key coupling step (postulated here to exist just distal to the alpha 1-adrenergic receptor yet proximal to the phospholipid turnover/Ca2+ mobilization steps) required for alpha-adrenergic-mediated fluid and electrolyte secretion from the aging rat exocrine parotid gland. Because the steps involved in this process are not fully elucidated, natural perturbation of rat parotid gland function should prove to be of particular value as a model toward clarification of the mechanisms of alpha-adrenergic signal transduction. It is now generally agreed that dopamine receptors are lost from the corpus striatum during aging in a variety of species, including humans. Most studies of age changes in striatal dopamine receptors have detected no alterations in binding affinity or dissociation constant (Kd). Only reduction in concentration (Bmax) with increasing age is apparent. Such receptor loss appears to be at least partially responsible for decreased dopamine stimulation of certain stereotypic behavioral responses and decreased neurotransmitter release. In addition, dopamine-sensitive adenylate cyclase (EC 4.6.1.1) decreases during senescence.