Distinct MAP Kinase Activation Patterns of Angiotensin and Cannabinoid Systems in SHR Astrocytes
ISBN or ISSN
The FASEB Journal
Publication Date / Copyright Date
Federation of American Societies for Experimental Biology (FASEB)
To determine the effect of exogenous Angiotensin (Ang) II and ACEA, both alone and in combination, on MAP kinase activation in astrocytes isolated from Spontaneously Hypertensive Rats (SHRs) and Wistar rats.
By activation of astroglial Ang type 1 receptor (AT1R) and Cannabinoid type 1 receptor (CB1R), Ang II and cannabinoids are able to exert potent effects on proliferation and neuroinflammation. An increase in phosphorylation states of MAP kinases such as ERK and p38, has been linked to several functions in astrocytes. Although crosstalk between the two receptors has been reported by us and several other groups, the consequences of this interaction at the level of MAP kinase activation has not been investigated.
Astrocytes were isolated from the brainstem and cerebellum of Spontaneously Hypertensive Rats (SHR) and normotensive Wistar rats. The cells were treated with 100 nM Ang II or 10 nM ACEA, both alone and in combination, for varying time periods and the extent of phosphorylation was measured using Western blotting.
Ang II treatment resulted in greater activation of MAP kinases in brainstem astrocytes, but not cerebellar astrocytes, of SHRs when compared to Wistar rats. ACEA treatement on the other hand, is associated with a greater activation of MAP kinases in brainstem, but not cerebellar, astrocytes of Wistar rats when compared to SHRs. Co-treatment of Ang II and ACEA resulted in greater activation of ERK and p38, than Ang II or ACEA treatments alone, in brainstem astrocytes isolated from both SHRs and Wistar rats. In cerebellar astrocytes however, co-treatment did not result in greater activation of MAP kinases than the treatments alone in both rat models.
Greater MAP kinase activation, by ACEA, in brainstem astrocytes of Wistar rats when compared to SHRs is suggestive of a potential diminished endocannabinoid tone in pathological conditions such as hypertensions. An augmentation of MAP kinase activation by the combination treatment in brainstem astrocytes, but not cerebellar astrocytes, is indicative of a potential dampening of one system by the other in cerebellar astrocytes. Our findings suggest that the crosstalk between AT1R and CB1R may differ depending on the brain area and the underlying pathological condition.
Support or Funding Information
NSU HPD: Grant # 335585
Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
angiotensin, astrocytes, cannabinoid systems, kinkase, Spontaneously Hypertensive Rats (SHRs)
Giridhar, Dhanush Haspula and Clark, Michelle A., "Distinct MAP Kinase Activation Patterns of Angiotensin and Cannabinoid Systems in SHR Astrocytes" (2017). Faculty Articles. 316.