Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic adenosine diphosphate ribose (cADPR) were first demonstrated to mobilize Ca2+ in sea urchin eggs. In the absence of direct measurements of these messengers, pharmacological studies alone have implicated these molecules as intracellular second messengers for specific cell surface receptor agonists. We now report that in mouse pancr...

G protein-regulated Ca2+ sensitivity of vascular contractile proteins plays an important role in cerebrovascular reactivity. The present study examines the intracellular mechanisms that govern G protein-regulated Ca2+ sensitivity in cerebral arteries of different size and age. We studied β-escin-permeabilized segments of common carotid, basilar, and middle cerebral arteries from nonpregnant adu...

The thiol reagent, thimerosal, has been shown to cause an increase in intracellular Ca2+ concentration ([Ca2+]i) in several cell types, and to cause Ca2+ spikes in unfertilized hamster eggs. Using single cell video-imaging we have shown that thimerosal evokes repetitive Ca2+ spikes in intact Fura-2-loaded HeLa cells that were similar in shape to those stimulated by histamine. Both thimerosal- a...

The effects of pharmacological activation and inhibition of protein kinase C (PKC) and temperature on the relationship between cytoplasmic Ca2+ and lumen diameter were studied in pressurized (50 mmHg) rat posterior cerebral arteries permeabilized with α-toxin. Increasing Ca2+ concentrations (30 nM-10 μM, 22°C) induced stable, concentration-dependent constrictions with a half-maximal effective c...

Partial bladder outlet obstruction (PBOO) alters the function of the whole bladder and produces specific alterations in the contractility of the bladder smooth muscle cell. The goal of this study was to test the hypothesis that PBOO affects smooth muscle contraction at the level of the receptor- and G protein-dependent increase in myofilament Ca2+ sensitivity. To address this question, we used ...

The effects of the cAMP pathway on the Ca2+ response elicited by phospholipase C-coupled receptor stimulations were studied in rat parotid cells. Although 1 μM isoproterenol (Iso) itself had no effect on the cytosolic Ca2+ concentration, the pretreatment with Iso potentiated Ca2+ responses evoked by phenylephrine. The potentiating effect of Iso was attributed to a shifting of the concentration-...

Intact and α-toxin-permeabilized longitudinal smooth muscle were mounted for measurement of force and myosin light chain phosphorylation. Galanin contracted intact jejunum with a half-maximum effective concentration of 9.2 ± 0.1 nM. Neither atropine, hexamethonium, guanethidine, nor tetrodotoxin affected the contraction. The contraction was also unaffected by depletion of intracellular Ca2+ or ...

Little is known about the signaling pathways involved in tr2-adrenergic receptor-mediated contraction of vascular smooth muscle. In the present study, we measured intracellular Ca21 ([Ca"2];), myosin light chain (MLC) phosphorylation, and myofilament Ca2' sensitivity during stimulation with the relatively selective cr2-agonist UK 14304. These effects were compared and contrasted with correspond...