# AGE-RELATED CHANGES IN ADRENERGIC CLINICAL PHARMACOLOGY

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 1992 · $193,931

## Abstract

The major objectives of this proposal are to define the nature, extent,
locus, and mechanism of age-related changes that occur in the human
peripheral adrenergic nervous system.  We postulate that age-related
changes are limited to innervated beta-adrenoceptors.

1) What age-related changes occur in the adrenergic nervous system of
humans? We postulate that the increased plasma norepinephrine
concentration in the elderly is due, in part, to a defect in adrenergic
neuronal uptake.  We plan to quantify neuronal uptake of norepinephrine
by determining the effect of desipramine on norepinephrine clearance.  We
also postulate that baroreceptor function is little changed with age. We
plan to test baroreceptor function by determining the plasma
norepinephrine response to pharmacologically induced changes in blood
pressure.
          Since our previous data indicate that age-related changes in
adrenergic function are limited to tissues that contain innervated
beta-adrenoceptors, we will investigate the function of the innervated
beta-adrenoceptor on human fat cells by determining catecholamine
stimulated lipolysis in vivo and in vitro. cAMP accumulation in response
to beta-adrenoceptor agonist, NaF, and forskolin will be determined in
isolated human adipocytes.
          We plan to study the pharmacokinetics and pharmacodynamics of
prazosin and the stereoisomers of propranolol in young and elderly
healthy volunteers as a followup to our previous studies.

2) What is the locus and mechanisms of these changes? Recent reports
suggest that endogenous adenosine may be responsible for reduced
beta-adrenoceptor responses in elderly animals.  We plan to test this
possibility in humans by determining the effect of theophylline on the
cardiac chronotropic response to beta-adrenoceptor stimulation.
          We will investigate the density of the beta-adrenoceptor on
each subpopulation of mononuclear leukocyte in order to explain our
previous observation that the elderly have a 2.5 fold increase in
beta-adrenoceptor density on their mononuclear cell membranes.  Cells
will be separated by binding of each population subtype to immunomagnetic
beads.
          We will characterize the human adipocyte beta-adrenoceptor
subtype(s) by determining receptor density,, antagonist affinity, and
coupling of the receptors to the catalytic subunit of adenylyl cyclase as
assessed by the ratio of the agonist high and low affinity states.
Iodinated pindolol will be used as the radioligand; agonists and
antagonists for competition binding studies will be based on their
specificity for the beta-adrenoceptor subtypes.  We will determine
whether age-related changes occur in post-receptor events in the human
adipocyte by assessing protein phosphorylation in response to
isoproterenol, forskolin, and dibutyryl cyclic AMP.  Cellular ATP will be
prelabelled with 32Pand phosphorylated peptides detected by
autoradiographs of SDS-PAGE gels.  These studies will be correlated with
the functional ...

## Key facts

- **NIH application ID:** 3121782
- **Project number:** 1R01AG009857-01A2
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** John G. Gerber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $193,931
- **Award type:** 1
- **Project period:** 1992-09-30 → 1997-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121782

## Citation

> US National Institutes of Health, RePORTER application 3121782, AGE-RELATED CHANGES IN ADRENERGIC CLINICAL PHARMACOLOGY (1R01AG009857-01A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121782. Licensed CC0.

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