AJP - Endocrinology and Metabolism, Vol 270, Issue 1 E96-100, Copyright © 1996 by American Physiological Society
Mechanism of verapamil calcium channel blockade-induced hyperprolactinemia
S. R. Kelley, T. J. Kamal and M. E. Molitch
Center for Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Verapamil, a phenylalkylamine calcium channel blocker, causes a doubling of
serum prolactin (PRL) levels in humans. To determine whether the mechanism
involved a decrease in the PRL response to dopamine (DA), we infused low
doses of DA, finding that the percent inhibition of PRL was not affected by
verapamil (max %decrements for 0.003, 0.01, and 0.03 microgram.kg-1.min-1
doses of DA, respectively, 86.7 +/- 19.1, 73.2 +/- 24.8, and 65.2 +/- 20.0%
without verapamil and 93.4 +/- 24.6, 79.7 +/- 14.9, and 58.0 +/- 18.1% with
verapamil). To determine whether the PRL elevation was due to a decrease in
hypothalamic generation of DA, we measured the inhibition of PRL by L-dopa
before and after inhibition of peripheral decarboxylase activity with
carbidopa. Without verapamil, L-dopa alone and carbidopa-L-dopa caused
similar maximum decreases in PRL levels of 83.2 +/- 2.5 and 80.3 +/- 2.0%,
respectively. With verapamil, the PRL maximum decrement with L-dopa was
85.2 +/- 2.7% and with carbidopa-L-dopa was 76.3 +/- 1.9% (P < 0.01). We
also found that dihydropyridine and benzothiazepine calcium channel
blockers had no effect on PRL. These results suggest that verapamil acts by
decreasing central DA generation, possibly through N-type calcium channels.
