To investigate delta-opioid receptor topography near the 3-position of [D-Pen2,D-Pen5]enkephalin (DPDPE), a series of small-group 3-position analogs of DPDPE have been synthesized and assayed for binding potencies and in vitro biological activities. L-Amino acid substitutions at this position are highly favored over D-amino acid substitutions, with the smallest, [L-Ala3]DPDPE (DPADPE), being the most favored in the series investigated. [L-Ala3]DPDPE is nearly as delta-potent and more delta-selective in both rat brain binding (18 nM vs [3H] [p-ClPhe4]DPDPE and mu/delta = 610) and peripheral bioassays (12 nM in the MVD and GPI/MVD = 4500) when compared to DPDPE (8.5 nM, mu/delta = 73 and 4.1 nM, GPI/MVD = 1800, respectively). Whereas DPDPE is a potent analgesic when given icv, [L-Ala3]DPDPE is only a weak analgesic. However, [L-Ala3]DPDPE has been found to antagonize DPDPE, but not Deltorphin II, in a moderately potent (pA2 = 5.7) and selective fashion in vivo. Thus, [L-Ala3]DPDPE is a fairly potent agonist at peripheral delta receptors and is a moderately potent (mixed) antagonist of delta 1 receptors in the brain. It appears that [L-Ala3]DPDPE does not interact in any significant manner with delta 2 or mu receptors in the brain.

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This study was undertaken as a part of the problem of predicting the irreversible thermal injury of skin. Of first importance in this problem is the determination of the temperatiire-time-depth history of skin subjected to an arbitrary thermal insult. Although this paper deals with radiant energy heating of skin, it is intended that the results may be applied to other modes of energy input, as well.The theoretical analysis of heat flow in irradiated skin is considered first, and the predicted responses of two models are presented. Methods are developed for the comparison of these theoretical predictions with experimental resultsJ these comparison schemes define the experimental procedures and materials which are next described in detail. Finally, the experimental results are presented, together with an evaluation of the constants of skin, whenever possible» While the experimental results failed to supply all the information necessary to compute the temperature response of skin to any arbitrary energy input, several important conclusions were reached. A most interesting result of the theoretical analysis is that the absorption pattern of radiation in skin may be determined directly by temperature measurements, and the data may be tested rigorously for their validity. Also, it is now possible to plan future experiments which will provide the necessary data which this study failed to supply. Most important is the indication that the desired prediction of thermal injury of skin may be achieved. ill

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