Effects of acetazolamide and 4-aminopyridine on CO2-induced slowly adapting pulmonary stretch receptor inhibition in rats.
Inhibitory responses of slowly adapting pulmonary stretch receptor (SAR) activity to CO(2) inhalation (maximal tracheal CO(2) concentration ranging from 9.5 to 12.5%) for approximately 60 s were examined before and after administration of acetazolamide (a carbonic anhydrase inhibitor) or 4-aminopyridine (4-AP, a K(+) channel blocker). The experiments were performed in 35 anesthetized, artificially ventilated rats after unilateral vagotomy. Sixty-eight of eighty-four SARs were inhibited by CO(2) inhalation. The SAR inhibition was attenuated by pretreatment with either acetazolamide (20 mg/kg, n = 10) or 4-AP (0.7 and 2.0 mg/kg, n = 10). In other series of experiments, stainings to show the existence of carbonic anhydrase (CA) enzymatic reaction were not found in the smooth muscle of either extrapulmonary or intrapulmonary bronchi. Protein gene product 9.5 (PGP 9.5)-immunoreactive SAR terminals to form leaflike extensions were found in the bronchioles at different diameters and were smooth-muscle-related receptors. But in the same sections, CA isozyme II-like (erythrocyte CA) immunoreactive SAR terminals were not identified. These results suggest that CO(2)-induced inhibition of SARs may be involved in the CA-dependent CO(2) hydration in addition to the activation of 4-AP sensitive K(+) currents.
Matsumoto
Shigeji
S
Department of Physiology, Nippon Dental University, School of Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. matsu-s@tky.ndu.ac.jp
Tanimoto
Takeshi
T
Yoshida
Shinki
S
Ikeda
Mizuho
M
Takeda
Mamoru
M
Saiki
Chikako
C
Shimazu
Yoshihito
Y
Aoba
Takaaki
T
Nasu
Masanori
M
Suzuki
Kazunori
K
D015761:4-Aminopyridine / Q000494:pharmacology*; D000086:Acetazolamide / Q000494:pharmacology*; D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D024402:Carbonic Anhydrase II / Q000502:physiology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011661:Pulmonary Stretch Receptors / Q000502:physiology*; D051381:Rats; D014132:Trachea / Q000166:cytology
D002257:Carbonic Anhydrase Inhibitors; D026902:Potassium Channel Blockers; D002245:Carbon Dioxide; D015761:4-Aminopyridine; D024402:Carbonic Anhydrase II; D000086:Acetazolamide