Activation of “silent” vasoconstrictive 5-HT1A receptors as a possible mechanism of synergism in angiotensin II and serotonin effect on vascular tone

Involvement of calmodulin in realization of vasoconstrictive effects of serotonin and norepinephrine

“…4). The kinetics of NAdr induced vascular con traction is untypical of α 1 AR excitation but analo gous to the kinetics reproduced during the 8 OH DPAT activation of 5HT1A receptors, namely, peri odic high amplitude fluctuations are observed after the maximum force of contraction has been reached (Kozhevnikova et al, 2011). The findings suggest the possibility of interaction between NAdr and 5HT1A receptors.…”

“…These results are in agreement with the previous data on the capability of the 5HT1A receptor agonist 8 OH DPAT to relax vessels con tracted by NAdr but not ET 1, vasopressin, or angio tensin II. On the contrary, its addition to the vessels precontracted by these vasoconstrictor compounds induces their further contraction (Kozhevnikova et al, 2009(Kozhevnikova et al, , 2011Kozhevnikova and Avdonin, 2010).…”

“…The α1 AR blocker prazosin (10 -7 M) does not suppress the vasocontrictive response to NAdr (10 -7 ) under its action on isolated rat aorta fragments after angio tensin II (10 -8 M) or vasopressin (10 -8 M) induced acti vation of 5HT1A receptors:Kozhevnikova et al, 2011 (a); unpublished data (b).…”

“…It has been revealed that sensitization of vasoconstrictor 5HT receptors develops at an invariable level of their expression and is a result of changes in the properties of these receptors. It has been shown that vasocon strictor 5HT1A receptors under physiological condi tions are in the latent (silent) state (Kozhevnikova et al, 2009(Kozhevnikova et al, , 2011Kozhevnikova and Avdonin, 2010). The trigger mechanism of their activation is excitation of endothelin (ETA), angiotensin (AT1A), or vaso pressin (V1A) receptors, but not α 1 adrenoceptors (α 1 AR).…”