Thrombin regulates nerve growth factor secretion from vascular, but not bladder smooth muscle cells.
The production of nerve growth factor (NGF) in peripheral organs may play a role in the pathophysiology of hypertension and in obstructive disorders of the bladder outlet. We have been examining the cellular processes of NGF delivery and secretion in smooth muscle. NGF secretion from vascular smooth muscle cells (VSMCs) cultured from genetically hypertensive (WKHT), hyperactive (WKHA), and a control Wistar rat strain were assayed using a two-site ELISA of the culture media. Bladder smooth muscle cells (BSMCs) from the Wistar strain were also studied. The serine protease, thrombin, increased NGF secretion from all types of VSMCs but had no effect on Wistar BSMCs. The thrombin-mediated increase in NGF secretion was prevented by actinomycin D and cycloheximide, suggesting that RNA transcription and protein synthesis are required. The effect of thrombin was additive with a phorbol ester-induced elevation in NGF secretion rates from 4 to 6 h and was attenuated by a 24-h downregulation of protein kinase C. These results suggest that extracellular protease activity may regulate NGF secretion in smooth muscle. Thrombin may act in response to vascular injury, increasing NGF secretion from VSMCs, initiating VSMC migration, and preparing the VSMCs for reinnervation following an insult.
Sherer
T B
TB
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Spitsbergen
J M
JM
Steers
W D
WD
Tuttle
J B
JB
D000818:Animals; D001011:Aorta; D007611:Aprotinin / Q000494:pharmacology; D002478:Cells, Cultured; D006629:Hirudins / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology*; D014357:Trypsin / Q000494:pharmacology; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism*
D006629:Hirudins; D007976:Leupeptins; D009414:Nerve Growth Factors; D011480:Protease Inhibitors; D007611:Aprotinin; D011493:Protein Kinase C; D014357:Trypsin; D013917:Thrombin; C032854:leupeptin