Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphodiesterase activator protein and troponin-C have been purified from rat testis and rabbit skeletal muscle, respectively. The two proteins appear to be structurally distinct since the activator protein migrates faster than troponin-C on sodium dodecyl sulfate-polyacrylamide gels. Each of the calcium-binding proteins will, however, substitute for the other in their respective biological systems. Testis activator protein forms a complex with rabbit muscle troponin subunits TnI and TnT soluble in low salt. This hybrid complex (AIT) can regulate rabbit skeletal muscle actomyosin ATPase activity. AIT regulation, although influenced by free Aa2+ levels, is distinct from that of native troponin. Likewise, muscle troponin-C can substitute for activator protein in the stimulation of cyclic nucleotide phosphodiesterase. Troponin-C will fully stimulate phosphodiesterase although its affinity is 600-fold lower than that of activator protein. Ca2+ regulation studies demonstrate that both proteins require micormolar levels of free Ca2+ to induce phosphodiesterase activation. Activator protein requires 1.2 x 10(6) M and troponin-C, 1.9 X 10(6) M free Ca2+ for half-maximal stimulation of phosphodiesterase. The biological cross-reactivity of these proteins supports the sequence homology recently reported by Watterson et al. (Watterson, D.M., Harrelson, W.G., Keller, P.M., Sharief, F., and Vanaman, T.C. (1976) J.Biol. Chem. 251, 4501-4513). In addition, this preliminary study suggests that this nonmuscle troponin-C-like protein potentially may function in other Ca2+-regulated cellular events in addition to its moculation of cyclic nucleotide levels.
 ...
PMID:Biological cross-reactivity of rat testis phosphodiesterase activator protein and rabbit skeletal muscle troponin-C. 19 60

The activities of several pivotal nucleotide metabolizing enzymes from the testis and vasal sperm of rats treated for 7 wk with 0, 20 or 30 mg X kg X day gossypol acetic acid were examined. Total testicular lactate dehydrogenase (LDH) activity increased 40% above control in the highest treatment group examined. However, the specific activity of the testis-specific isozyme of LDH, LDH-C4, decreased to 50 and 20% of control in the 20 and 30 mg X kg X day treatment groups, respectively. Basal soluble adenylate cyclase from a 100,000 X g supernatant of testis homogenate exhibited a 25% decrease in activity only in the 30-mg treatment group. Basal adenylate cyclase activity in the testicular membrane fraction increased 20 to 30% above control in response to gossypol administration. Testis membranes from the 20- and 30-mg treatment group exhibited a 2- and 4-fold greater activation of adenylate cyclase by guanine nucleotides. In vitro dose-response curves showed a half-maximal inhibitory concentration (IC50) for inhibition of soluble testicular adenylate cyclase by gossypol of 400 microM in each treatment group. Caudal epididymal sperm adenylate cyclase activity decreased to 25% of control levels in gossypol-treated animals, and the in vitro sensitivity of the enzyme to the inhibitory effects of gossypol increased 4-fold. IC50 values for gossypol inhibition of sperm adenylate cyclase decreased from 200 microM in control animals to 75 and 50 microM in the 20 and 30 mg X kg X day treatment groups, respectively. Cyclic adenosine 3':5' monophosphate phosphodiesterase activity in caudal sperm increased 6-fold in the 20- and 30-mg treatment groups. These results demonstrate that nucleotide metabolizing enzymes in sperm are major targets for the actions of gossypol and provide a possible mechanism for the inhibition of normal sperm function by this compound.
 ...
PMID:Gossypol modulation of nucleotide metabolizing enzymes in the reproductive tract of male rats. 609 38