cyclic-gmp and neferine

To further investigate the relaxation mechanism of neferine (Nef), a bis-benzylisoquinoline alkaloid extracted (isolated) from the green seed embryo of Nelumbo nucifera Gaertn in China, on rabbit corpus cavernosum tissue in vitro.. The effects of Nef on the concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in isolated and incubated rabbit corpus cavernosum tissue were recorded using 125I radioimmunoassay.. The basal concentration of cAMP in corpus cavernosum tissue was 5.67 +/- 0.97 pmol/mg. Nef increased the cAMP concentration in a dose-dependent manner (P < 0.05), but this effect was not inhibited by an adenylate cyclase inhibitor (cis-N-[2-phenylcyclopentyl]azacyclotridec-1-en-2-amine, MDL-12, 330A) (P > 0.05). The accumulation of cAMP induced by prostaglandin E1 (PGE1, a stimulator of cAMP production) was also augmented by Nef in a dose-dependent manner (P < 0.05). The basal concentration of cGMP in corpus cavernosum tissue is 0.44 +/- 0.09 pmol/mg. Nef did not affect this concentration of cGMP, either in the presence or in the absence of a guanyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) (P > 0.05). Also, sodium nitroprusside (SNP, a stimulator of cGMP production)-induced cGMP production was not enhanced by Nef (P > 0.05).. Nef, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting phosphodiesterase activity.

Topics: Animals; Benzylisoquinolines; Cyclic AMP; Cyclic GMP; Drugs, Chinese Herbal; Erectile Dysfunction; In Vitro Techniques; Male; Muscle Relaxation; Muscle, Smooth; Nelumbo; Penile Erection; Penis; Phytotherapy; Plant Extracts; Rabbits; Radioimmunoassay; Seeds; Vasodilator Agents

Neferine (Nef), a hypotensive agent with antiarrythmic action, is a dibenzyl isoquinoline alkaloid isolated from a Chinese medicinal herb (Nelumbo nucifera Gaertn). Its effects on platelet aggregation and TXA2/PGI2 and cAMP/cGMP balance were studied with methods of turbidimetry and RIA. Nef was shown to significantly inhibit rabbit platelet aggregation induced by ADP, collagen, arachidonic acid (AA) and platelet-activating factor (PAF) with IC50 of 16, 22, 193 and 103 mumol.L-1, respectively. Nef was found to increase vascular 6-keto-PGF1 alpha and platelet cAMP levels in dose-dependent manner, but inhibit AA stimulated TXA2 release from platelets. Nef showed no significant effect on the platelet cGMP level. The results suggest that the mechanism of Nef on platelet aggregation is related to regulation of TXA2/PGI2 and cAMP/cGMP balance.

Topics: 6-Ketoprostaglandin F1 alpha; Alkaloids; Animals; Aorta, Thoracic; Benzylisoquinolines; Blood Platelets; Cyclic AMP; Cyclic GMP; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Rats; Thromboxane B2