ROLE OF HISTAMINE IN GASTRIC SECRETION: FROM DISCOVERY TO CLINICAL APPLICATION (A Tribute Leon Popielski To 150-Anniversary From His Birth)
Professor of Lviv National Medical University (formerly known as Jan Kazimierz Lemberg University), Ukraine, Leon Popielski was the ﬁ rst to recognize that histamine stimulated gastric acid secretion 100 years ago, at 1916. He produced over one hundred publications and founded Lviv’s experimental gastroenterology school (Koskowski, 1931), and strong pharmacology tradition. He is less well known today than he deserves to be. Popielski began his scientiﬁ c career at the Military Medical Academy in St Petersburg, then dominated by I. Pavlov. In 1901, he published work indicating the existence of a peripheral ‘reﬂ ex center’ controlling gastric secretion (Popielski, 1901). His ﬁ ndings contradicted the prevailing ‘nervism’ theory of Pavlov, who had supervised Popielski’s PhD thesis. Perhaps not surprisingly this caused friction between them. Pavlov then started a process to verify Popielski’s results, which was later described in Boris Babkin’s memoirs. The results were conﬁ rmed thereby establishing the idea that processes other than conditional-reﬂ exes, and in particular peripheral mechanisms, also controlled gastric secretion. Popielski’s work on histamine was carried out in Lviv during the World War I period, although published only later. He clearly showed that histamine was a strong stimulant of gastric acid secretion. His PhD student W. Koskowski subsequently introduced the histamine test for gastric secretion in patients, which in a somewhat modiﬁ ed form, was used clinically for many decades in Poland at 1930’s. In the 1960’s and early 1970’s, Professor Sir James Black, at what was then Smith, Kline and French, brilliantly extended Popielski’s model of the role of histamine in gastric secretion through the development and use of a new class of antisecretory drug – the H2 receptor antagonists (Black et al., 1972). These proved the essential role of histamine in stimulating acid secretion. An early example, cimetidine, became the ﬁ rst truly blockbuster drug, and revolutionised the treatment of peptic ulcer disease. At 21st century the novel gastric acid blockers – inhibitors of proton pump (PPI) were included in standard protocols for treatment several acid-related diseases. Long-term gastric acid suppression has been associated with different complications in gastric mucosa. Moreover, the roles of gastric acid inhibition in extragastral damage manifestation and several groups have reported abnormal proliferation in gastrointestinal tract during long-term treatment by IPP or H2 receptor antagonists. In the past 10 years due to these side effects, there is a need to study dual actions of histamine on gastrointestinal mucosa. Progress of scientiﬁ c thought allowed to identify numerous histamine receptors (H1-H4) and their multifunctional meaning, and in that way to facilitate appearing of new medicine, which have totally changed treatment tactic of gastroenterological and neurogical diseases. Popielski’s work provides a clear example of how basic physiological research can be translated into the clinic for patient beneﬁ t. Scientiﬁ c portrait of L. Popielski doesn’t limit in his scientiﬁ c and studying publications, he is an author of numerous publications, dedicated to the healthy way of life. Intellectual courage, belief in the reliability of obtained results and incredible assiduity of L. Popielski, deserve to be respected nowadays.
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