Pertussis toxin‐sensitive G i ‐proteins and intracellular calcium sensitivity of vasoconstriction in the intact rat tail artery

We studied the involvement of pertussis toxin (PTX)‐sensitive G‐proteins in the sensitivity of arterial constriction to intracellular calcium ([Ca 2+ ] i ) mobilization. Vasoconstriction was measured in vitro in perfused, de‐endothelialized rat tail arteries loaed with the calcium‐sensitive dye, fura‐2 and treated or not with PTX (30–1000 ng ml −1 ). Arteries were stimulated with noradrenaline (NA, 0.1–100 μ M ) or KCl (15–120 m M ). KCl elicited a smaller vasoconstrictor response (E max =94±8 mmHg) than NA (E max =198±9 mmHg) although [Ca 2+ ] i mobilization was similar (E max =123±8 and 135±7 n M for KCl and NA, respectively). PTX (1000 ng ml −1 ) had no effect on [Ca 2+ ] i mobilization but lowered NA‐ (but not KCl‐) induced vasoconstriction (E max =118±7 mmHg). G i/o ‐proteins were revealed by immunoblotting with anti‐G iα and anti‐G oα antibodies in membranes prepared from de‐endothelialized tail arteries. [α 32 P]‐ADP‐ribosylation of G‐proteins by PTX (1000 ng ml −1 ) was demonstrated in the intact rat tail artery (pixels in the absence of PTX: 3150, presence: 25053). In conclusion, we suggest that smooth muscle cells possess a PTX‐sensitive G i ‐protein‐mediated intracellular pathway which amplifies [Ca 2+ ] i sensitivity of contraction in the presence of agonists such as NA.British Journal of Pharmacology (2000) 131 , 1337–1344; doi: 10.1038/sj.bjp.0703703