ABSTRACT
The stimulation by nicotine of intramural nerves and the role of ATP and vasoactive intestinal peptide (VIP) as inhibitory transmitters were studied in the isolated taenia of the guinea-pig caecum. Nicotine (4-32 microM) caused transient, concentration-dependent relaxations which were unaffected by atropine, prazosin or sotalol. Drugs with membrane-stabilizing activity, such as dl-propranolol (0.5 microM), d-propranolol (0.5 microM) or lidocaine (10 microM) antagonized the nicotine-induced relaxation without modifying the response to electrical field stimulation. Similar results were obtained with the cyclooxygenase inhibitor, indomethacin (2.8 microM). Nucleotide pyrophosphatase (0.5 U/ml), which hydrolyzes ATP to AMP, reversibly inhibited the response to nicotine but the response to field stimulation was not decreased. Nicotine evoked a calcium-dependent release of VIP, which was blocked by tetrodotoxin (1 microM), d-propranolol (0.5 microM) or, as previously shown, by apamin (0.2 microM). The finding that nicotine-induced relaxation was accompanied by the neuronal release of VIP is compatible with the possibility that VIP is an inhibitory transmitter but is not definitive evidence, since it could have been due to the stimulation of distinct populations of nerves by nicotine.
Subject(s)
Colon/physiology , Nicotine/pharmacology , Vasoactive Intestinal Peptide/metabolism , Animals , Apamin/pharmacology , Colon/innervation , Colon/metabolism , Female , Guinea Pigs , In Vitro Techniques , Male , Pyrophosphatases/physiology , Stimulation, ChemicalABSTRACT
The effect of adenosine on an internal calcium store which can be released by carbachol to produce a transient contraction in Ca2+-free solution was investigated in the taenia depolarized by high K+. The carbachol contraction in Ca2+-free solution was increased by the preceding application of adenosine (3 X 10(-5) to 10(-3) M), an effect which was mimicked by ATP, but not by the slowly degradable analog alpha, beta-methylene ATP. The P1-purinoceptor antagonist 8-phenyltheophylline inhibited the increase caused by adenosine without modifying the carbachol contraction in controls. It is concluded that stimulation of an extracellular P1-purinoceptor increases an internal store of calcium, which might contribute to the relaxation induced by adenosine in the taenia.
Subject(s)
Adenosine/pharmacology , Calcium/metabolism , Intestines/drug effects , Muscle, Smooth/drug effects , Adenosine Triphosphate/pharmacology , Animals , Egtazic Acid/pharmacology , Female , Guinea Pigs , In Vitro Techniques , Intestinal Mucosa/metabolism , Male , Muscle Contraction/drug effects , Muscle, Smooth/metabolism , Muscle, Smooth/physiology , Receptors, Neurotransmitter/drug effects , Receptors, PurinergicABSTRACT
The effects of adenosine on the calcium contraction of high K+ (low Na+)-depolarized preparations, as well as on the uptake and release of 45Ca, were studied in the guinea-pig taenia coli. Adenosine (10(-4)-10(-3) M) inhibited the calcium contraction of high K+-depolarized preparations, an effect which was mimicked by ATP (10(-4)-10(-3) M), but not by the slowly degradable ATP analog, adenosine 5'-alpha, beta-methylene triphosphate. The high K+ -stimulated calcium influx measured by 3-6 min exposures to 45Ca was not changed by adenosine (10(-3) M). In high K+ solution, adenosine (10(-3) M) increased the fractional rate of efflux of 45Ca-labelled preparations. These results indicate that stimulation of calcium extrusion, but not inhibition of calcium influx, may take part in the mechanism of the relaxation induced by adenosine in the taenia.
Subject(s)
Adenosine/pharmacology , Calcium/metabolism , Muscle, Smooth/physiology , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/pharmacology , Animals , Biological Transport, Active/drug effects , Calcium/pharmacology , Colon/drug effects , Colon/physiology , Female , Guinea Pigs , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Potassium/pharmacologyABSTRACT
The hyperpolarizations in response to ATP and adenosine in the guinea-pig taenia coli, measured by the sucrose-gap technique at room temperature, were compared in solutions of modified ionic composition. ATP hyperpolarization was increased in low chloride and in low potassium, but was reduced to 12% of control in calcium-free solution on second application of the agonist. The response to adenosine, however, was decreased in low chloride, unchanged in low potassium and was 45% of control in calcium-free solution. The different mechanisms for ATP and adenosine hyperpolarization provide evidence for the presence of separate receptors.
Subject(s)
Adenosine Triphosphate/pharmacology , Adenosine/pharmacology , Muscle, Smooth/drug effects , Animals , Calcium/pharmacology , Chlorides/pharmacology , Colon/drug effects , Female , Guinea Pigs , In Vitro Techniques , Male , Membrane Potentials/drug effects , Potassium/pharmacology , Receptors, Cell Surface/metabolism , Receptors, PurinergicABSTRACT
The effects of ATP, bradykinin (BK) and electrical stimulation of intramural non-adrenergic non-cholinergic nerves (NS) were compared in four smooth preparations. In the guinea-pig taenia caeci and rat duodenum, ATP (10(-7)-5 x 10(-5) M) and BK (5 x 10(-10)-10(-7) M) closely mimicked the response to NS. The relaxations to BK, but not to ATP or NS, were inhibited by carboxypeptidase B (3-15 U/ml) and apamin (10(-8)-5 x 10(-8) M) prevented the relaxations to all three stimuli. BK contracted the guinea-pig distal colon whereas ATP and NS caused inhibition. In the guinea-pig bladder, ATP and NS induced rapid phasic contractions whereas BK caused tonic contractions. In the latter two preparations, incubation with indomethacin failed to reveal any BK relaxation. In view of its failure to mimic the nerve-mediated response in two of the tissues, and of its selective inhibition by carboxypeptidase B in the other two, BK is less likely to be the transmitter in non-adrenergic non-cholinergic nerves supplying smooth muscle.
