Luminal purinergic regulatory mechanisms of tracheal ciliary beat frequency

To investigate the modulation of tracheal ciliary beat frequency (CBFt) by purine nucleotides and nucleosides acting on luminal receptors, aerosolized ATP, GTP, AMP-PNP, GMP-PNP, adenosine, and guanosine were each administered separately to the tracheal lumen in eucapnically ventilated, barbiturate-anesthetized beagles. Four studies were conducted in each of seven dogs from a cohort of eight dogs. The CBFt responses were measured on the right lateral surface of the mid-trachea using heterodyne mode correlation analysis laser light scattering. Aerosolized 10(-6) M and 10(-5) M ATP stimulated CBFt from the baseline of 5.9 +/- 1.4 Hz to maxima of 12.1 +/- 1.4 Hz and 13.3 +/- 1.6 Hz, respectively, while the same corresponding ATP-analogue (AMP-PNP) concentrations stimulated baseline CBFt to maxima of 12.7 +/- 4.1 Hz and 18.1 +/- 2.1 Hz, respectively. Similarly, 10(-6) M and 10(-5) M GTP stimulated baseline CBFt to maxima of 14.8 +/- 1.1 Hz and 12.8 +/- 4.6 Hz, respectively. The corresponding GTP-analogue (GMP-PNP) concentrations stimulated CBFt to maxima of 14.5 +/- 2.1 Hz and 18.8 +/- 4.4 Hz, respectively. Prior delivery of 10(-5) M adenosine reduced all these nucleotide-induced stimulatory responses. Prior delivery of 10(-5) guanosine partially reduced the GTP- and the GMP-PNP-induced stimulatory responses. These data demonstrate that nucleotides and nucleosides modulate CBFt through specific P2 and P1 purinergic receptors on the luminal surface, thus providing a direct mechanism within the airways to enhance the transport of mucus.