Analysis of vasoactive intestinal peptide receptors and the G protein regulation of adenylyl cyclase in seminal vesicle membranes from streptozotocin-diabetic rats.
The present report describes the status of the vasoactive intestinal peptide (VIP) receptor/effector system of signal transduction in seminal vesicle from streptozotocin (STZ)-treated rats. STZ-treatment modified the binding parameters of the high-affinity sites for VIP in seminal vesicle: 0.78 +/- 0.10 and 2.54 +/- 0.30 nM for the dissociation constant (Kd) in control and diabetic rats, respectively; 0.07 +/- 0.01 and 0.15 +/- 0.03 pmol VIP/mg protein for the maximum binding capacity (Bmax) in control and diabetic rats, respectively. It was associated with a reduced potency of VIP on the stimulation of adenylyl cyclase activity in the diabetic state (ED50 = 64.0 +/- 20.0 nM) as compared to control (ED50 = 9.5 +/- 4.3 nM). In contrast, the stimulatory effects of GTP, Gpp[NH]p and forskolin on the enzyme activity were not modified in diabetic rats. The levels of G-protein subunits in rat seminal vesicle were studied by immunoblot of alpha s and alpha i subunits: whereas alpha i-subunit levels did not vary, those corresponding to alpha s subunit decreased after STZ treatment. In diabetic rats, low concentrations of Gpp[NH]p failed to inhibit forskolin-stimulated adenylyl cyclase activity, suggesting the absence of functional Gi in this condition. In conclusion, present results show a decrease in the sensitivity of the VIP receptor/effector system in seminal vesicle membranes from STZ-treated rats suggesting a physiopathological role for VIP in the seminal neuropathy observed in diabetes.
Rodriguez-Pena
M S
MS
Departamento de Bioquímica y Biología Molecular, Hospital Ramón y Cajal, Universidad de Alcalá, Alcalá de Henares, Spain.
Guijarro
L G
LG
Juarranz
M G
MG
Rodriguez-Henche
N
N
Bajo
A M
AM
Aguado
F
F
Prieto
J C
JC
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism*; D012669:Seminal Vesicles / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D013311:Streptozocin; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology
D018005:Receptors, Vasoactive Intestinal Peptide; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D014660:Vasoactive Intestinal Peptide; D013311:Streptozocin; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases