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S A Doggrell

Publications and source records attributed to S A Doggrell.

At least 109 records · Page 6Linked to original sources
PubMed1981

Prazosin selectively inhibits the responses to field stimulation in the rat vas deferens.

The effects of prazosin on contractile responses of the epididymal and prostatic halves of the rat vas deferens have been studied. In the epididymal half responses to acetylcholine were not altered by hexamethonium, 100 microM, but were inhibited by atropine, 10 nM. Prazosin, 100 nM, had no effect on maximal or submaximal responses to acetylcholine or methacholine. In the presence of cocaine, 10 microM, prazosin 10 and 100 nM, reduced the magnitude of the maximal twitch and sustained responses to field stimulation in the epididymal and prostatic halves of the vas deferens. Submaximal responses at all frequencies of stimulation and to exogenously applied noradrenaline were also inhibited by prazosin. Thus all responses to field stimulation of the epididymal and prostatic halves of the vas deferens are susceptible to selective alpha 1-adrenoceptor blockade with low concentrations of prazosin.

Acetylcholine↗
PubMed1981

The use of the rat right ventricle strip in studies on noradrenergic transmission.

1. The possibility of using contractility studies with the rat right ventricle strip to assess the effects of drugs on all aspects of noradrenergic transmission has been examined. 2. The force of the contractile responses to field stimulation at 0.5 and 2, but not 5 Hz, markedly decreased with time. About 55% of the tissues responded directly to (-)-isoprenaline, 1 X 10(-6)M (123 tissues from 220 tested) in the absence of other stimuli. In these tissues the force of the contractile responses remained constant and the rate increased with time. Thus it is essential to provide time controls in studies with rat right ventricle. 3. Under conditions in which the responses to (-)-isoprenaline, 1 X 10(-6)M, alone were unaffected the responses to field stimulation at 5 Hz were inhibited by 66 and 86% by 9 X 10(-6)M tetrodotoxin and 1 X 10(-5)M guanethidine, respectively. (+/-)-Propranolol and timolol (both at 1 X 10(-6)M), but not phentolamine, 1 X 10(-6)M, inhibited responses to (-)-isoprenaline, 1 X 10(-6)M alone and responses to field stimulation at 5 Hz. This demonstrates that the responses to field stimulation are largely due to activation of noradrenergic nerves, the released noradrenaline acting at postsynaptic beta-adrenoreceptors. 4. Although nortriptyline is a potent inhibitor of the neuronal uptake of noradrenaline, at 1 X 10(-6)M it had no effect on the contractile responses to field stimulation at 5 Hz and inhibited responses to (-)-isoprenaline, 1 X 10(-6)M, alone and at a higher concentration (1 X 10(-5)M) nortriptyline abolished both responses. It is suggested that the rat ventricle preparation may be useful in examining the effects of drugs on noradrenergic transmission in the heart.

Adrenergic beta-Antagonists↗
PubMed1981

Effect of antimuscarinic agents on the contractile responses to cholinomimetics in the rat anococcygeus muscle.

1 The effects of antimuscarinic agents alone and in the presence of neostigmine on the contractile responses to exogenously applied cholinomimetics or (-)-noradrenaline were studied in the rat anococcygeus muscle.2 Atropine (1 x 10(-9) -1 x 10(-6)M) alone, in the presence of hexamethonium (1 x 10(-4)M), or phentolamine (1 x 10(-6)M), inhibited responses to acetylcholine but not to (-)-noradrenaline. The inhibitory effect with the higher concentrations of atropine (1 x 10(-8) - x 10(-6)M), was seen as an increase in the slopes of the concentration-response curves. Atropine (1 x 10(-8)M) alone inhibited the responses to methacholine and carbachol without altering the slopes of the concentration-response curves.3 Homatropine (1 x 10(-6)M) alone had no effect on responses to (-)-noradrenaline and inhibited responses to acetylcholine and methacholine. The inhibitory effect on responses to acetylcholine but not to methacholine, included an increase in the slopes of the concentration-response curves.4 Neostigmine (1 x 10(-6)M) alone had no effect on responses to (-)-noradrenaline and potentiated responses to acetylcholine and methacholine. The potentiating effect included an increase in the slopes of the concentration-response curves.5 In the presence of neostigmine (1 x 10(-6)M), atropine (1 x 10(-9)M - 1 x 10(-6)M) caused a parallel concentration-dependent shift of the concentration-response curves to acetylcholine. The pA(2) values, in the presence of neostigmine, were independent of the concentration of atropine and of the agonist (acetylcholine, methacholine, or carbachol) used. In the presence of neostigmine (1 x 10(-6)M), homatropine (1 x 10(-6)M) also failed to alter the slopes of the concentration-response curves to acetylcholine and was approximately 100 times less potent than atropine as an antimuscarinic agent.6 These results illustrate that, in the rat anococcygeus muscle, it is necessary to inhibit acetylcholinesterase before determining the relative potencies of antagonists at muscarinic receptors.

Animals↗
PubMed1981

The postsynaptic effects of antidepressant drugs in the rat anococcygeus muscle.

The effects of antidepressants of tricyclic (amitriptyline, nortriptyline, protriptyline, doxepin, imipramine, and desipramine) and atypical (maprotiline, nomifensine, tandamine, viloxazine, CGP 6085A, and YM-08054-1) structures on contractile responses to exogenously applied acetylcholine and (-) noradrenaline were studied in rat isolated anococcygeus muscle previously incubated with 6-hydroxydopamine. Atropine, amitriptyline, protriptyline, doxepin, imipramine, maprotiline and nortriptyline inhibited contractile responses to acetylcholine whereas desipramine, nomifensine, tandamine, viloxazine, CGP 6085A and YM 08054-1 did not. The contractile responses to (-)-noradrenaline were inhibited by low concentrations of tricyclic antidepressants and by higher concentrations of the atypical agents. These results illustrate that, in the preparation, the order of potency of antidepressants as muscarinic and as postsynaptic alpha-adrenoceptor antagonists is similar. The ability of tricyclic, but not atypical agents, to increase the concentration of noradrenaline bound to postsynaptic alpha-adrenoceptors may be severely limited by the antagonistic effect these agents have at this receptor.

Acetylcholine↗
PubMed1980

Effect of mianserin on noradrenergic transmission in the rat anococcygeus muscle.

1 The effects of mianserin on the accumulation of (-)-[(3)H]-noradrenaline and on contractile responses to field stimulation, exogenously applied (-)-noradrenaline, and to tyramine were studied in the rat anococcygeus muscle.2 Mianserin (10(-9) to 10(-5) M) and nortriptyline (10(-9) to 10(-5) M) inhibited the accumulation of (-)-[(3)H]-noradrenaline. In this aspect mianserin had a similar potency to nortriptyline, the most potent tricyclic antidepressant in inhibiting noradrenaline accumulation in this tissue.3 Mianserin 10(-9) or 10(-8) M alone had no effect on contractile responses to field stimulation and to (-)-noradrenaline but inhibited the responses to tyramine. The responses to field stimulation at low frequencies and to (-)-noradrenaline were potentiated by 10(-7) and 10(-6) M mianserin. It is suggested that the inhibitory effect mianserin has on neuronal accumulation is primarily responsible for these effects. Mianserin 10(-5) M inhibited responses to field stimulation and to (-)-noradrenaline.4 In the presence of nortriptyline (10(-6) M), the contractile responses to field stimulations were potentiated by mianserin (10(-8), 10(-7) and 10(-6) M), 10(-8) M being the most potent in this aspect. Mianserin 10(-8), 10(-7), 10(-6) and 10(-5) M had a similar inhibitory effect on responses to (-)-noradrenaline. In the absence of neuronal uptake, the potentiating effect of mianserin on responses to field stimulation may be due to antagonism at presynaptic alpha-adrenoceptors. In the presence of 10(-6) M nortriptyline, 10(-5) M mianserin abolished responses to field stimulation.5 Following incubation of the tissue in the presence of 6-hydroxydopamine (10(-3) M for 3 h), mianserin (10(-7), 10(-6) and 10(-5) M) nortriptyline (10(-7) and 10(-6) M) and phentolamine (5 x 10(-8) and 5 x 10(-7) M) inhibited contractile responses to (-)-noradrenaline. This illustrates the ability of these agents to inhibit the responses to noradrenaline at a postsynaptic site. The inhibitory effect was dose-related with nortriptyline and phentolamine; this illustrates the ability of these agents to antagonize postsynaptic alpha-adrenoceptors. The inhibitory effect observed with mianserin was not dose-related. This suggests that in addition to its reported ability to antagonize postsynaptic alpha-adrenoceptors, mianserin may have another post-synaptic action at the level of, or distal to, the alpha-adrenoceptor.6 These results illustrate that, in the rat anococcygeus muscle, mianserin is a potent inhibitor of noradrenaline accumulation and may be an antagonist at presynaptic alpha-adrenoceptors. Mianserin also inhibits the responses to exogenously applied noradrenaline in this tissue by an action or actions at the level of, or distal to, the postsynaptic alpha-adrenoceptor.

Animals↗
PubMed1980

The occurrence of postsynaptic alpha- and beta-adrenoceptors in the guinea-pig gall bladder.

1 Guinea-pig gall bladder strips were contracted by (-)-noradrenaline, 10(-5) M, and by field stimulation at 5 Hz (in the absence or presence of 10(-6) M atropine) and relaxed to 10(-5) M (-)-isoprenaline. (-)-Adrenaline, 10(-5) M, predominantly contracted, but sometimes relaxed, this preparation. 2 In the presence of 10(-6) M phentolamine, contractions to (-)-noradrenaline and to (-)-adrenaline were reversed to relaxations. The relaxations produced by (-)-isoprenaline were unaltered. In the presence of 10(-6) M propranolol, contractions to (-)-noradrenaline increased in magnitude, relaxations to (-)-adrenaline were reversed to contractions, and relaxations to (-)-isoprenaline were abolished. These results demonstrate the presence of postsynaptic alpha-adrenoceptors which mediate contractions, and postsynaptic beta-adrenoceptors which initiate relaxations, in the guinea-pig gall bladder. 3 The contractile responses to continuous field stimulation for 5 min at 5 Hz in Krebs solution alone were reduced in magnitude by propranolol, 10(-6) M. In the presence of 10(-6) M atropine (added to eliminate the cholinergic component of the response), propranolol, 10(-6) M, had no effect on responses to stimulation at 5 Hz. Thus propranolol reduced the response to cholinergic stimulation in this tissue; the basis of this effect is unclear. In the absence or presence of atropine (10(-6) M), the responses to 5 Hz were smaller in magnitude in the presence than absence of phentolamine, 10(-6) M. This suggests that the responses to field stimulation of the guinea-pig gall bladder may, in part, be due to the release of endogenous noradrenaline which acts at postsynaptic alpha-adrenoceptors.

Animals↗
PubMed1980

The effects of time and indomethacin on contractile responses of the guinea-pig gall bladder in vitro.

1. The effects of time and of indomethacin on contractile responses of the guinea-pig gall bladder were studied in vitro. 2. The tissues contracted to field stimulation at 5 Hz (in the absence and presence of atropine 10(-6) M). (-)-noradrenaline (10(-5) M), acetylcholine (10(-5) M), and adenosine 5'-triphosphate (ATP, 10(-4) M); the magnitude of the contractile responses increased with time. 3. (-)-Isoprenaline 10(-5) M either relaxed (17 of 23 preparations tested) or had no effect on gall bladder strips. 4. The responses of strips of guinea-pig gall bladder to field stimulation at 5 Hz (in the absence or presence of atropine 10(-6) M), (-)-noradrenaline (10(-5) M), and acetylcholine (10(-5) M) obtained 4 h 45 min after setting up the tissue were reduced following incubation with indomethacin (7.9 x 10(-6) M for 1 h). The responses to (-)-isoprenaline (10(-5) M) and to ATP (10(-4) M) were abolished by incubation with indomethacin. 5. These results suggest that, in the guinea-pig gall bladder in vitro, the magnitude of the contractile responses to field stimulation at 5 Hz, (-)-noradrenaline (10(-5) M), and acetylcholine (10(-5) M) and the ability of the tissue to respond to (-)-isoprenaline (10(-5) M) and ATP (10(-4) M), may be dependent on the synthesis of a prostaglandin-like substance.

Acetylcholine↗
PubMed1980

Accumulation and overflow of 3H following incubation of the guinea-pig gall bladder with [3H]-noradrenaline.

1 Strips of guinea-pig gall bladder readily accumulate (3)H following incubation in the presence of 5 x 10(-8) M (-)-[(3)H]-noradrenaline. This accumulation was reduced by lowering the incubation temperature (from 37 degrees to 23 degrees C), by cocaine (10(-6) M), by nortriptyline (10(-8), 10(-6) and 10(-4) M) and following incubation of the tissues with 6-hydroxydopamine (10(-3) M for 3 h). At 10(-6) M, (-)-noradrenaline and (-)-adrenaline, but not (-)-isoprenaline, inhibited the accumulation of (3)H.2 Following preloading of strips of guinea-pig gall bladder with 3.6 x 10(-7) M (-)-[(3)H]-noradrenaline for 1 h, the spontaneous overflow of (3)H was observed. Cocaine (10(-4) M), nortriptyline (10(-6) M), (-)-isoprenaline (10(-5) M), acetylcholine (10(-5) M) and adenosine 5'-triphosphate (ATP, 10(-4) M) had no effect on the spontaneous overflow of (3)H. KCl (10(-1) M), (-)-noradrenaline (10(-5) M), (-)-adrenaline (10(-5) M), and tyramine (10(-5) M) increased the overflow of (3)H. These results illustrate similar characteristics of the guinea-pig gall bladder to other noradrenergically-innervated tissues in accumulating and releasing (3)H following incubation in the presence of [(3)H]-noradrenaline.3 Following incubation in the presence of 3.6 x 10(-7) M (-)-[(3)H]-noradrenaline, field stimulation, at 5 Hz, of strips of gall bladder, in the absence or presence of 10(-6) M atropine, increased the overflow of (3)H and, simultaneously, induced contractions. The contractile responses to 5 Hz were smaller in the presence than in the absence of 10(-4) M lignocaine. Lignocaine (10(-4) M) reduced the overflow of (3)H evoked by field stimulation at 5 Hz. It is suggested that the contractile responses to 5 Hz are due to nerve stimulation and that the increased overflow of (3)H is due to the stimulation of noradrenergic nerves.4 The overflow of (3)H evoked by field stimulation at 5 Hz was unaltered and increased by propranolol (10(-6) M) and phentolamine (10(-6) M), respectively. Clonidine (5 x 10(-5) M) had no effect in the absence but reduced the amount of (3)H which overflowed in response to field stimulation at 5 Hz in the presence of 10(-6) M atropine. The contractile responses to field stimulation at 5 Hz were reduced by phentolamine (10(-6) M) or clonidine (5 x 10(-6), 10(-5) and 5 x 10(-5) M) whether or not atropine (10(-6) M) was present. These results illustrate the presence of postsynaptic alpha-adrenoceptors and suggest the presence of presynaptic alpha-adrenoceptors in the gall bladder of the guinea-pig.

Animals↗
PubMed1979

Mianserin potentiates responses to acetylcholine in the rat anococcygeus muscle.

In the rat anococcygeus muscle, mianserin (1 and 10 muM) increased the magnitude of the maximal contractile responses to acetylcholine and carbamylcholine without affecting the maximal responses to (--)-noradrenaline. The potentiating effect of mianserin on responses to acetylcholine was maintained in the presence of 5muM phentolamine, following 6-hydroxy dopamine incubation of the tissues (1 mM for 3h) and in the presence of 1 muM nortriptyline. It is suggested that mianserin increases the sensitivity to acetylcholine by an action at the level of, or distal to, the cholinergic receptor.

Acetylcholine↗
PubMed1978

Effect of labetalol on the accumulation and release of noradrenaline in rat ventricle.

In rat ventricular tissue, labetalol inhibited the accumulation of (-)-[3H]noradrenaline and released [3H] following preloading with (-)[3H]noradrenaline. Cocaine (30 micrometer) inhibited the release observed with tyramine (5 micrometer) and beta-phenethylamine (5 micrometer) but not that observed with labetalol (5 micrometer). Reserpine pretreatment of the animals abolished the release observed with labetalol (5 and 50 micrometer). Labetalol primarily increased the loss of deaminated metabolites of noradrenaline. It is suggested that labetalol may release (-)-noradrenaline from the vesicles.

Animals↗
PubMed1978

Release of noradrenaline by labetalol in the rat anococcygeus muscle.

The effects of labetalol on the accumulation and spontaneous release of (--)-[3H]noradrenaline, and on contractile responses to exogenously applied (--)-noradrenaline were studied in the isolated anococcygeus muscle of the rat. 1. Labetalol (3 x 10(-7)--10(-4)M) inhibited the accumulation of (--)-[3H]noradrenaline. 2. Labetalol (10(-6)--10(-4)M) and guanethidine (6 x 10(-6) M) increased the spontaneous release of [3H] following incubation of the muscle with (--)-[3H]noradrenaline. Nortriptyline (10(-6) M) had no effect on the spontaneous release of [3H], antagonised the increased release of [3H] produced by 6 x 10(-6) M guanethidine but not that observed with 10(-5) M labetalol. Labetalol (5 x 10(-6) M) markedly increased the loss of tritiated deminated metabolites with little change in the loss of (--)-[3H]noradrenaline. 3. Labetalol (10(-7)--10(-5)M), alone or in the presence of 10(-6) M nortriptyline, had no effect on contractile responses to (--)-noradrenaline. 4. Following pretreatment with 6-hydroxydopamine (10(-3)M for 3 h) to deplete endogenous noradrenaline stores, labetalol (10(-7)--10(-5) M) inhibited responses to exogenously applied (--)-noradrenaline. 5. These results suggest that, in the rat anococcygeus muscle, labetalol is a noradrenaline releasing agent and an alpha-adrenoceptor antogonist.

Animals↗
PubMed1978

Effects of drugs on the accumulation and spontaneous release of noradrenaline in the rat anococcygeus muscle.

1 The ability of drugs to inhibit noradrenaline accumulation and to release noradrenaline was studied in the isolated anococcygeus muscle of the rat. 2 Noradrenaline, tyramine, 2-amino,6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), 2-amino,6,7-dimethoxy-1,2,3,4-tetrahydronaphthalene (dimethyl ADTN), and 5-hydroxytryptamine were all potent inhibitors of noradrenaline accumulation and potent releasers of noradrenaline. ADTN was accumulated by the rat isolated anococcygeus muscle. 3 Amphetamine and desipramine were potent inhibitors of noradrenaline accumulation but poor releasers of noradrenaline. 4 Methoxamine, oxymetazoline, acetylcholine, and angiotensin were poor inhibitors of noradrenaline accumulation and did not release noradrenaline. 5 The mechanism of action of these drugs is discussed.

Animals↗