Functional innervation of pig tracheal smooth muscle: neural and non-neural mechanisms of relaxation.
In pig tracheal smooth muscle (TSM), the isometric tension responses to electrical field stimulation (EFS) were compared to exogenous peptides, vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP), as well as to the nicotinic agonist dimethylphenyl piperazinium chloride (DMPP). The objectives of this study were to understand the mechanisms of nonadrenergic, noncholinergic relaxations of pig TSM and identify some putative candidate substances mediating the neural inhibitory response. In strips of TSM obtained from 6- to 12-week-old pigs set up in vitro in organ baths in Kreb's solution, EFS resulted in frequency-dependent contractions that were abolished by 1 microM atropine or 0.1 microM tetrodotoxin (TTX). Addition of DMPP (20-100 microM) resulted in a transient, atropine-sensitive contraction, which quickly desensitized. EFS failed to elicit any further contractions, but the tissues responded to carbachol. In tissues exposed to DMPP and contracted with carbachol, EFS elicited frequency-dependent relaxations that were unaffected by 1 microM propranolol, abolished by TTX and partially inhibited by omega-conotoxin. At the peak of carbachol-induced contraction, addition of DMPP resulted in rapid relaxation reversing spontaneously to base line, with no significant relaxation to further addition of DMPP. DMPP-induced relaxations were unaffected by TTX or omega-conotoxin. These tissues readily relaxed to 10(-8) M VIP. In carbachol precontracted tissues, VIP elicited concentration-dependent relaxations that quickly desensitized. However, these tissues readily relaxed to DMPP. CGRP produced only weak relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)
Kannan
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MS
Department of Veterinary Biology, College of Veterinary Medicine, University of Minnesota, St. Paul.
Johnson
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DE
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000294:innervation*; D009569:Nitric Oxide / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000294:innervation*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D020960:omega-Conotoxins
D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide; D015740:Calcitonin Gene-Related Peptide