The benzodiazepine receptor: functional complexity

muscle s, but 2-methylthioadenosine was a weak partial agonist. Furthermore, 8bromo substitution caused a loss of inhibitory activity in gut s and coronary smooth muscle ts. OI substituents may promote a syn conformation ill-suited for binding s'ts. However such a modification strongly shifts the parine dipole moment and reduces its strength s'ts. providing two possible explanations for loss of activity. A number of workers have emphasized the requirement for a primary or secondary 6-amino group for agonist activity s'ts'16. Alteration of the C6 substituem usually reduces smooth muscle inhibitory properties, with the exception of certain hydrophobic N6 substituents. which were shown to preserve or enhance inhibition of smooth muscle ~s''. inosine and guanosine, and their mono, phosphates, lack the 6-amino group and exhibited little if any activity on a variety of preparations of gut s and the vasculature ~7. However, in preparations of the guinea-pig trachea, guanosine and inosine caused a greater inhibition than adenosine but sm.-prisingly their responses were antagonized by dipyridamole, which potentiated ~esponses to adenosine. Thus, inosin¢ and guanosine may be acting intraceilulafly and adenosine extracellularly raising the possibility that the adenosine receptor in trachea may yet be the same as in other tissues. The future for purine pharmacology is undoubtedly very bright. New, highly potent compounds will be synthesized which may prove of considerable clinical ~,,lue. it is hoped that other studies will further evaluate the role of endogenous purines as hormones and neurohormones. In this respect new potent specific antagonists are needed especially for the P2/ATP receptor.