Geoffrey Burnstock, our friend and magister: the diadenosine polyphosphate connection

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REVIEW ARTICLE

Geoffrey Burnstock, our friend and magister: the diadenosine polyphosphate connection María-Teresa Miras-Portugal 1

&

Javier Gualix 1

Received: 31 August 2020 / Accepted: 15 September 2020 # Springer Nature B.V. 2020

Abstract Development of science needs the cooperation of many creative brains. Sometimes, ideas on a specific area get suddenly exhausted and then it is the time for a privileged mind to think in a different way and reach the turning point to introduce a new paradigm. This happened to Geoffrey Burnstock, a heterodox thinker and nonconformist scientist that has been the paladin of purinergic signalling since 1972, opening neuroscience to the understanding of organs and tissues functioning and development of a new pharmacology. This review summarizes the contribution of our group to the understanding of the role of the diadenosine polyphosphates, ApnA, as signalling molecules, describing their tissue and organ distribution, their transport and storage in secretory vesicles and their release and interaction with purinergic receptors. We also have to acknowledge the friendly and kindly support of Professor Burnstock that showed a great interest in the field from our initial findings and actively stimulated our efforts to establish the extracellular roles and biological significance of these dinucleotides. Keywords Diadenosine polyphosphates . Dinucleotides . ApnA . Secretory vesicles . Synaptic terminals

Introduction By 1988, our research area focused on chromaffin cell secretion and their exocytotic control. We were lucky because, in addition to catecholamines, ATP and ADP, we found the presence in chromaffin cells of other natural compounds, previously described in platelets [1], such as adenine dinucleotides, now known as diadenosine polyphosphates, diadenosine tetraphosphate (Ap 4 A) and diadenosine pentaphosphate (Ap5A) being the most prominent [2]. Our group was curious about the functional role of these compounds, and I decided to attend the meeting on “Purine Nucleosides and Nucleotides in Cell Signalling,” which took place in Maryland (USA), on September 1989. There, Professor Alexander Ribeiro introduced me to Professor Geoffrey Burnstock. We had a very fruitful talk and I was convinced that it was worth trying to find an answer

* Javier Gualix [email protected] María-Teresa Miras-Portugal [email protected] 1

Department of Biochemistry and Molecular Biology, Veterinary Faculty, Complutense University of Madrid, Madrid, Spain

concerning the physiological role and molecular biology events of ApnA. Once back to Madrid, the effect of diadenosine polyphosphates on catecholamine secretion from isolated chromaffin cells was studied. These compounds significantly increased basal secretion of catecholamines and had an absolute requirement for extracellular Ca2+, as it happens with classic neurotransmitters. Once organized the results, the manuscript was sent to British Journal of Pharmacology. It was accepted without any problem, except the classical English style, and was published