G-protein regulation of adenylate cyclase activity in rat prostatic membranes after chronic ethanol ingestion

• Published in: The Prostate Vol. 36; no. 4; pp. 226 - 234
• Main Authors: Juarranz, Maria G., Guijarro, Luis G., Bodega, Guillermo, Prieto, Juan C.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01-09-1998; Wiley-Liss
• Subjects: adenylate cyclase; Adenylyl Cyclases - metabolism; alcoholism; Alcoholism - metabolism; Alcoholism - pathology; Animals; Atrophy; Biological and medical sciences; Colforsin - pharmacology; Cyclic AMP - metabolism; Enzyme Activation - drug effects; Ethanol - toxicity; GTP Phosphohydrolases - metabolism; GTP-Binding Proteins - chemistry; GTP-Binding Proteins - metabolism; guanine nucleotide-binding regulatory protein; Guanylyl Imidodiphosphate - pharmacology; In Vitro Techniques; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Prostate - drug effects; Prostate - metabolism; Prostate - pathology; Protein Conformation; rat prostate gland; Rats; Rats, Wistar; Receptors, Vasoactive Intestinal Peptide - drug effects; Receptors, Vasoactive Intestinal Peptide - metabolism; Signal Transduction; Urinary system; vasoactive intestinal peptide; Vasoactive Intestinal Peptide - metabolism; β-adrenergic receptor; Ethanol; Rat; Enzyme; Toxicity; Alcoholism; Peptide hormone; Rodentia; Phosphorus-oxygen lyases; Exploration; Male; Lyases; Male genital system; Neuropeptide; Adenylate cyclase; Vertebrata; Gastrointestinal hormone; Mammalia; Animal; VIP; Prostate; G protein
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/(SICI)1097-0045(19980901)36:4<226::AID-PROS3>3.0.CO;2-D

BACKGROUND
The possibility that long‐term ethanol ingestion might alter either vasoactive intestinal peptide (VIP) content, VIP binding to membrane receptors, G‐protein levels or adenylate cyclase activity in rat prostate was tested, as ethanol produces serious alterations in the hypothalamic‐pituitary‐gonadal axis and several modifications on different elements on signal transduction pathways in other systems.
METHODS
Prostatic membranes from control and ethanol‐treated (for 4 weeks) rats were used to study adenylate cyclase stimulation as well as for the immunodetection of stimulatory (αs) and inhibitory (αi1–2) G‐protein subunits. Studies on VIP binding and cross‐linking to receptors were performed using [125I]VIP. Prostatic VIP content was estimated by radioimmunoassay. GTPase activity was quantified by measuring the amount of 32Pi released from [γ‐32P]GTP.
RESULTS
Chronic ethanol ingestion resulted in an increased presence of VIP in the rat prostate without any change on the VIP receptor/effector system in this gland. By contrast, the basal adenylate cyclase activity as well as the dose‐dependent stimulation of this enzyme by either the nonhydrolyzable GTP analogue Gpp(NH)p or the β‐adrenergic agonist isoproterenol were enhanced in prostatic membranes after ethanol intake. Moreover, an increase in the content of G‐protein subunits (αs and αi1–2) was observed without any change in GTPase activity in this condition. These modifications were accompanied by a significant decrease in rat prostate weight and, consequently, the height of the secretory epithelium in this gland.
CONCLUSIONS
Considering the role of VIP in the mechanisms of secretion and cell proliferation in the prostate, the observed increases in the prostatic content of VIP and G‐protein subunits make conceivable that VIP and cAMP signal transduction could be involved in the atrophy of the rat prostate and in the alterations in the composition of seminal fluid that appear in the alcoholic syndrome. Prostate 36:226–234, 1998. © 1998 Wiley‐Liss, Inc.