The relationship among retinoid structure, affinity for retinoic acid-binding protein, and ability to respecify pattern in the regenerating axolotl limb.
To further our understanding of the action of retinoids on the respecification of pattern in the regenerating axolotl limb we have studied the relative potencies of a range of synthetic and natural retinoids administered locally to the blastema. Alterations in the polar end group of the retinoic acid (RA) molecule to produce esters, the alcohol, or the aldehyde abolish the ability of the molecule to respecify pattern. On the other hand, alterations of the ring or side chain to produce the synthetic retinoids arotinoid and TTNPB considerably increases the potency of the molecule to respecify pattern--TTNPB is at least 100X more potent than retinoic acid. To examine the role of cellular retinoic acid-binding protein (CRABP) in the respecification process we determined the relative binding affinities of these retinoids for CRABP. These data correlated well with the respecification series: retinoids which showed no affinity for CRABP did not respecify pattern and those which did show affinity for CRABP did respecify pattern. Furthermore the most potent retinoid, TTNPB, has a higher affinity for CRABP than RA itself. This suggests that CRABP may be playing an important role in the action of RA on pattern formation in the regenerating limb.
Keeble
S
S
National Institute for Medical Research, London, United Kingdom.
Maden
M
M
D000287:Administration, Topical; D000557:Ambystoma; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005121:Extremities / Q000502:physiology; D009024:Morphogenesis / Q000187:drug effects; D018168:Receptors, Retinoic Acid; D012038:Regeneration / Q000187:drug effects*; D012176:Retinoids / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D012176:Retinoids