Biochemical mechanism of caffeine tolerance

Arch Pharm (Weinheim). 1991 May;324(5):261-7. doi: 10.1002/ardp.19913240502.

Abstract

Most of the biological actions of caffeine are possibly mediated through its antagonistic effects to adenosine. Adenosine activates an inhibitory GTP-binding protein (Gi). One of the physiological actions of Gi is the inhibition of cAMP formation. Caffeine overcomes this action thus leading to elevation of cAMP. Firing of neurons and the release of neurotransmitters is also inhibited by adenosine. Caffeine overcomes this effect, thus producing increased CNS-activity. During long term administration of caffeine many functions of the organism develop tolerance including cardiovascular and central nervous systems. Present evidence suggests that caffeine tolerance following continuous severe coffee ingestion is the response of the body against caffeine through the upregulation of adenosine receptors.

Publication types

  • Review

MeSH terms

  • Adenosine / antagonists & inhibitors
  • Animals
  • Caffeine / pharmacology*
  • Drug Tolerance
  • Humans

Substances

  • Caffeine
  • Adenosine