H1-histaminergic activation of catecholamine release by chromaffin cells

Bovine adrenal medullary chromaffin cells, prelabeled with [3H]norepinephrine, released a large proportion of cellular 3H-labeled catecholamines (CAs) when stimulated with nicotine, K+, histamine, gamma-aminobutyric acid (GABA) and several peptidic hormones [bradykinin, angiotensin II, thyrotropin releasing hormone (TRH) and neurotensin]. The histamine-induced response was dose dependent and occurred through H1 histaminergic receptors. Quantitatively and temporally the histamine- and nicotine-induced responses differed. Nicotine, during the first minutes, induced a large increase of [3H]CAs, but this response was desensitized rapidly. In contrast, histamine initially provoked a smaller release of [3H]CAs than nicotine but, with prolonged exposure (hours), a much greater response was found with histamine. Moreover, little desensitization was observed with histamine even during extended stimulation. External Ca2+ was obligatory for the histamine response, and both inorganic (Co2+ and Ni2+) and organic (verapamil, nifedipine and D-600) Ca2+ channel blockers significantly reduced release of [3H]CAs. These studies suggest that histamine as well as certain other neuroactive substances could play an important role in the physiology and biochemistry of adrenal medullary chromaffin cells.