Tags

Type your tag names separated by a space and hit enter

Modulation of relaxant responses evoked by a nitric oxide donor and by nonadrenergic, noncholinergic stimulation by isozyme-selective phosphodiesterase inhibitors in guinea pig trachea.
J Pharmacol Exp Ther. 1995 Mar; 272(3):997-1004.JP

Abstract

Nonadrenergic, noncholinergic relaxations were elicited by field stimulation (1-16 Hz, 1 msec, 8 V for 15 sec) of guinea pig trachea desensitized with capsaicin (3 microM), pretreated with atropine (1 microM), propranolol (1 microM), indomethacin (3 microM) and treated with alpha-chymotrypsin (2 U/ml) and contracted with 3 microM histamine. The effect of the phosphodiesterase (PDE) isozyme selective inhibitors siguazodan (PDE III-selective), rolipram (PDE IV-selective), denbufylline (PDE IV-selective) and zaprinast (PDE V-selective) was examined on the relaxant responses to field stimulation and on relaxations elicited by the nitric oxide donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1). The response to field stimulation in the presence of alpha-chymotrypsin (the putative nitric oxide component), at all the frequencies tested, was potentiated significantly by the PDE IV inhibitors rolipram (1 and 10 microM) and denbufylline (3 and 10 microM) as were responses to SIN-1. The PDE V inhibitor zaprinast (30 microM) potentiated relaxations elicited by field stimulation at 8 and 16 Hz and also potentiated responses to SIN-1. The PDE III inhibitor siguazodan (1 microM), however, was without effect on relaxant responses to field stimulation or to SIN-1. These results suggest that the nitric oxide component of the nonadrenergic, noncholinergic relaxant response is mediated primarily via cyclic AMP whose action is inactivated by a PDE IV isozyme and also by cyclic GMP which is inactivated by a PDE V isozyme.

Authors+Show Affiliations

Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7891355

Citation

Ellis, J L., and N D. Conanan. "Modulation of Relaxant Responses Evoked By a Nitric Oxide Donor and By Nonadrenergic, Noncholinergic Stimulation By Isozyme-selective Phosphodiesterase Inhibitors in Guinea Pig Trachea." The Journal of Pharmacology and Experimental Therapeutics, vol. 272, no. 3, 1995, pp. 997-1004.
Ellis JL, Conanan ND. Modulation of relaxant responses evoked by a nitric oxide donor and by nonadrenergic, noncholinergic stimulation by isozyme-selective phosphodiesterase inhibitors in guinea pig trachea. J Pharmacol Exp Ther. 1995;272(3):997-1004.
Ellis, J. L., & Conanan, N. D. (1995). Modulation of relaxant responses evoked by a nitric oxide donor and by nonadrenergic, noncholinergic stimulation by isozyme-selective phosphodiesterase inhibitors in guinea pig trachea. The Journal of Pharmacology and Experimental Therapeutics, 272(3), 997-1004.
Ellis JL, Conanan ND. Modulation of Relaxant Responses Evoked By a Nitric Oxide Donor and By Nonadrenergic, Noncholinergic Stimulation By Isozyme-selective Phosphodiesterase Inhibitors in Guinea Pig Trachea. J Pharmacol Exp Ther. 1995;272(3):997-1004. PubMed PMID: 7891355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of relaxant responses evoked by a nitric oxide donor and by nonadrenergic, noncholinergic stimulation by isozyme-selective phosphodiesterase inhibitors in guinea pig trachea. AU - Ellis,J L, AU - Conanan,N D, PY - 1995/3/1/pubmed PY - 1995/3/1/medline PY - 1995/3/1/entrez SP - 997 EP - 1004 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 272 IS - 3 N2 - Nonadrenergic, noncholinergic relaxations were elicited by field stimulation (1-16 Hz, 1 msec, 8 V for 15 sec) of guinea pig trachea desensitized with capsaicin (3 microM), pretreated with atropine (1 microM), propranolol (1 microM), indomethacin (3 microM) and treated with alpha-chymotrypsin (2 U/ml) and contracted with 3 microM histamine. The effect of the phosphodiesterase (PDE) isozyme selective inhibitors siguazodan (PDE III-selective), rolipram (PDE IV-selective), denbufylline (PDE IV-selective) and zaprinast (PDE V-selective) was examined on the relaxant responses to field stimulation and on relaxations elicited by the nitric oxide donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1). The response to field stimulation in the presence of alpha-chymotrypsin (the putative nitric oxide component), at all the frequencies tested, was potentiated significantly by the PDE IV inhibitors rolipram (1 and 10 microM) and denbufylline (3 and 10 microM) as were responses to SIN-1. The PDE V inhibitor zaprinast (30 microM) potentiated relaxations elicited by field stimulation at 8 and 16 Hz and also potentiated responses to SIN-1. The PDE III inhibitor siguazodan (1 microM), however, was without effect on relaxant responses to field stimulation or to SIN-1. These results suggest that the nitric oxide component of the nonadrenergic, noncholinergic relaxant response is mediated primarily via cyclic AMP whose action is inactivated by a PDE IV isozyme and also by cyclic GMP which is inactivated by a PDE V isozyme. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7891355/Modulation_of_relaxant_responses_evoked_by_a_nitric_oxide_donor_and_by_nonadrenergic_noncholinergic_stimulation_by_isozyme_selective_phosphodiesterase_inhibitors_in_guinea_pig_trachea_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7891355 DB - PRIME DP - Unbound Medicine ER -