cyclic-gmp and tetrandrine

The aim of this study was to further investigate the relaxation mechanism of tetrandrine (Tet), a bis-benzylisoquinoline alkaloid isolated from the Chinese medicinal herb-root of Stephania tetrandra S Moore, on rabbit corpus cavernosum tissue in vitro. The effects of Tet on the concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in isolated and incubated rabbit corpus cavernosum tissue were recorded by means of (125)I radioimmunoassay. The basal concentration of cAMP in corpus cavernosum tissue was 5.67 +/- 0.97 pmol mg(-1). Tet 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 E(1) (PGE(1), a stimulator of cAMP production) was also augmented by Tet in a dose-dependent manner (p < 0.05). The basal concentration of cGMP in corpus cavernosum tissue is 0.44 +/- 0.09 pmol mg(-1). Tet did not affect this concentration of cGMP, neither in the presence nor the absence of a guanyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) (p > 0.05). Further, sodium nitroprusside (SNP, a stimulator of cGMP production)-induced cGMP production was not enhanced by Tet (p > 0.05). Tet, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting PDEs activity.

Topics: Animals; Benzylisoquinolines; Calcium Channel Blockers; Cyclic AMP; Cyclic GMP; In Vitro Techniques; Male; Penis; Rabbits

The rat pineal gland with its circadian noradrenaline-regulated melatonin rhythm is an excellent model for studying adrenergic signal transduction with respect to cAMP and cGMP formation. The stimulatory G(s) proteins play a well-established role in this process. In contrast, the potential roles of the inhibitory G(i) proteins, the functionally unclear other G(o) proteins, and a number of G protein subtypes are not known. The present study examines the effects on beta(1)- and beta(1)-plus-alpha(1)-stimulated cAMP and cGMP formation of a number of G protein modulators in rat pinealocyte suspension cultures. The effects of the nitric oxide donor sodium nitroprusside on cGMP were also examined. The results showed that drugs that activate G proteins of the G(i)/G(o) family, i.e., pertussis toxin, mastoparan, and compound 48/80, had no effect on unstimulated, isoproterenol (beta(1))-stimulated, or combined isoproterenol/phenylephrine (beta(1)-plus()-alpha(1))-stimulated cAMP and cGMP accumulation. However, in this experimental paradigm, the inhibitors of sulfhydryl G proteins (N-ethylmaleimide) and those of phospholipase A2-related G proteins (isotetrandrine) exerted a clear inhibitory effect. Sodium-nitroprusside-stimulated cGMP accumulation was also inhibited. These results confirm a previous report that members of the G(i)/G(o) family, which are present in the rat pineal gland, do not play a major role in adrenergic signal transduction. The new finding that sulfhydryl G proteins and phospholipase A2-associated G proteins exert a clear stimulatory effect on adrenergic signal transduction suggests that they are subtypes of G(s) proteins.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Alkaloids; Animals; Arylamine N-Acetyltransferase; Benzylisoquinolines; Cyclic AMP; Cyclic GMP; Ethylmaleimide; GTP-Binding Proteins; Intercellular Signaling Peptides and Proteins; Isoproterenol; Male; Nitric Oxide; Nitroprusside; p-Methoxy-N-methylphenethylamine; Peptides; Pertussis Toxin; Phenylephrine; Phospholipases A; Phospholipases A2; Pineal Gland; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic; Signal Transduction; Sulfhydryl Reagents; Virulence Factors, Bordetella; Wasp Venoms