Cyclic AMP regulates mRNA expression of alpha-1d and alpha-2a adrenergic receptors in cultured human corpus cavernosum smooth muscle cells

While the physiological effects of contractile (e.g. norepinephrine) and re laxatory (e,g, PGE1, forskolin) agents on corpus cavernosum smooth muscle t one have been characterized, the regulation of alpha adrenergic receptor mR NA expression in erectile tissue remains to be investigated. The goal of th is study was to investigate the modulation of alpha-1 and alpha-2 adrenergi c receptor mRNA expression in cultured human corpus cavernosum smooth muscl e cells in response to increased intracellular cAMP induced by prostaglandi n El and forskolin. Human corpus cavernosum smooth muscle cells were incubated for 24 h with or without PGE1 (5.7 mu M), forskolin (10 mu M) or an admixture of both. Tota l RNA was prepared from the cultures, Expression of alpha-id adrenergic rec eptor, alpha-2a adrenergic receptor and m2 muscarinic acetylcholine recepto r was determined by RNase protection assays, Loading was normalized by RNas e protection of the housekeeping gene, cyclophilin A. The relative abundanc e of mRNAs was quantitated by scanning densitometry. Treatment of human corpus cavernosum smooth muscle cells with PGE1 or forsk olin resulted in decreased mRNA expression of alpha-id and alpha-2a adrener gic receptors and m2 muscarinic acetylcholine receptor when compared to unt reated cells. Combinations of PGE1 and forskolin produced a more pronounced decrease in mRNA than either agent alone. PGE1 and forskolin increased int racellular levels of cAMP in human corpus cavernosum smooth muscle cells an d combinations of both agents produced a more pronounced increase in cAMP s ynthesis, These results suggest that cAMP modulates the expression of alpha adrenergic receptors, one of the principal contractile receptor systems in the corpora cavernosa, These observations further support the concept that erectile function is a balance between contractile and relaxatory processe s, which in turn regulate structure and function of the corpora cavernosa.