Mitogenic effects of ATP on vascular smooth muscle cells vs. other growth factors and sympathetic cotransmitters
Erlinge, David LU
; Yoo, H
; Edvinsson, Lars
LU
; Reis, D J
and Wahlestedt, C
(1993)
In American Journal of Physiology - Heart and Circulatory Physiology
265(4).
p.1089-1097
- Abstract
- The sympathetic nervous system has been shown to exert a trophic influence on vascular smooth muscle cells (VSMC). Therefore, we studied the growth-regulating effects of the sympathetic cotransmitters ATP, neuropeptide Y (NPY), and norepinephrine (NE). ATP in concentrations of 1-100 microM greatly increased the incorporation of [3H]thymidine in VSMC from rat aorta and vena cava. ATP also increased cell number and total protein content. The maximal effect on [3H]thymidine incorporation was greater than for epidermal growth factor (20 ng/ml) or insulin (1 microgram/ml) and approximately one-half that of 10% fetal calf serum. The potency series of other nucleotides and analogues of ATP was ATP > beta, gamma-methyleneATP (AMP-PCP) > ADP... (More)
- The sympathetic nervous system has been shown to exert a trophic influence on vascular smooth muscle cells (VSMC). Therefore, we studied the growth-regulating effects of the sympathetic cotransmitters ATP, neuropeptide Y (NPY), and norepinephrine (NE). ATP in concentrations of 1-100 microM greatly increased the incorporation of [3H]thymidine in VSMC from rat aorta and vena cava. ATP also increased cell number and total protein content. The maximal effect on [3H]thymidine incorporation was greater than for epidermal growth factor (20 ng/ml) or insulin (1 microgram/ml) and approximately one-half that of 10% fetal calf serum. The potency series of other nucleotides and analogues of ATP was ATP > beta, gamma-methyleneATP (AMP-PCP) > ADP > adenosine > alpha, beta- methyleneATP (AMP-CPP) > 2-methylthioATP, indicating involvement of a P2 receptor, however, it does not meet proposed pharmacological criteria of either the P2x or P2y subclass. Several proposed P2 receptor antagonists were without effect. The effect of ATP could be mediated by a "nucleotide receptor," since UTP also stimulated [3H]thymidine incorporation. In our model, there was a strong correlation between the mitogenic effects of ATP, AMP-CPP, AMP-PCP, and UTP and their ability to stimulate influx of extracellular Ca2+ (Ca2+o). Moreover, the mitogenic effect of ATP was increased by high concentrations of Ca2+o. Taken together with data showing the lack of involvement of several other second-messenger systems, this indicates a critical role for Ca2+o in mediating the mitogenic effects of ATP. Amiloride, known to inhibit the action of several growth factors, also inhibited ATP-induced mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1107187
- author
- Erlinge, David
LU
; Yoo, H
; Edvinsson, Lars
LU
; Reis, D J
and Wahlestedt, C
- organization
- publishing date
- 1993
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Physiology - Heart and Circulatory Physiology
- volume
- 265
- issue
- 4
- pages
- 1089 - 1097
- publisher
- American Physiological Society
- external identifiers
-
- pmid:7694483
- scopus:0027133991
- ISSN
- 1522-1539
- language
- English
- LU publication?
- yes
- id
- c584bd30-ce47-4315-9fc2-5b1cb0609c17 (old id 1107187)
- alternative location
- http://ajpheart.physiology.org/cgi/reprint/265/4/H1089
- date added to LUP
- 2016-04-01 16:35:57
- date last changed
- 2024-01-11 11:04:50
@article{c584bd30-ce47-4315-9fc2-5b1cb0609c17,
abstract = {{The sympathetic nervous system has been shown to exert a trophic influence on vascular smooth muscle cells (VSMC). Therefore, we studied the growth-regulating effects of the sympathetic cotransmitters ATP, neuropeptide Y (NPY), and norepinephrine (NE). ATP in concentrations of 1-100 microM greatly increased the incorporation of [3H]thymidine in VSMC from rat aorta and vena cava. ATP also increased cell number and total protein content. The maximal effect on [3H]thymidine incorporation was greater than for epidermal growth factor (20 ng/ml) or insulin (1 microgram/ml) and approximately one-half that of 10% fetal calf serum. The potency series of other nucleotides and analogues of ATP was ATP > beta, gamma-methyleneATP (AMP-PCP) > ADP > adenosine > alpha, beta- methyleneATP (AMP-CPP) > 2-methylthioATP, indicating involvement of a P2 receptor, however, it does not meet proposed pharmacological criteria of either the P2x or P2y subclass. Several proposed P2 receptor antagonists were without effect. The effect of ATP could be mediated by a "nucleotide receptor," since UTP also stimulated [3H]thymidine incorporation. In our model, there was a strong correlation between the mitogenic effects of ATP, AMP-CPP, AMP-PCP, and UTP and their ability to stimulate influx of extracellular Ca2+ (Ca2+o). Moreover, the mitogenic effect of ATP was increased by high concentrations of Ca2+o. Taken together with data showing the lack of involvement of several other second-messenger systems, this indicates a critical role for Ca2+o in mediating the mitogenic effects of ATP. Amiloride, known to inhibit the action of several growth factors, also inhibited ATP-induced mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)}},
author = {{Erlinge, David and Yoo, H and Edvinsson, Lars and Reis, D J and Wahlestedt, C}},
issn = {{1522-1539}},
language = {{eng}},
number = {{4}},
pages = {{1089--1097}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology - Heart and Circulatory Physiology}},
title = {{Mitogenic effects of ATP on vascular smooth muscle cells vs. other growth factors and sympathetic cotransmitters}},
url = {{http://ajpheart.physiology.org/cgi/reprint/265/4/H1089}},
volume = {{265}},
year = {{1993}},
}