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D C Bolser

Publications and source records attributed to D C Bolser.

35 records · Page 2Linked to original sources
PubMed1993

GABAB receptors in the lung.

gamma-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the mammalian CNS, is also found in peripheral tissues, including the lung. Recent pharmacological studies using selective ligands for GABAA and GABAB receptors demonstrate that of these two, the GABAB receptor is the important receptor subtype controlling lung functions. GABAB agonists inhibit a variety of responses in the airways, including neuronally induced cholinergic- and tachykinin-mediated smooth muscle contraction, microvascular leakage, anaphylactic bronchospasm and cough. Because these conditions are seen in certain respiratory diseases, such as asthma, a selective GABAB agonist may have therapeutic potential for the treatment of this respiratory disorder.

Anaphylaxis↗
PubMed1993

Antitussive effects of GABAB agonists in the cat and guinea-pig.

1. GABAB agonists inhibit neuronal processes which are important in the pathogenesis of airway disease, such as bronchospasm. Cough is a prominent symptom of pulmonary disease, but the effects of GABAB agonists on this airway reflex are unknown. Experiments were conducted to determine the antitussive effect of GABAB receptor agonists in comparison to the known antitussive agents, codeine and dextromethorphan. 2. Unanaesthetized guinea-pigs were exposed to aerosols of 0.3 mM capsaicin to elicit coughing, which was detected with a microphone and counted. Cough also was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was recorded from electromyograms of respiratory muscle activity. 3. In guinea-pigs, the GABAB agonists baclofen and 3-aminopropyl-phosphinic acid (3-APPi) produced dose-dependent inhibition of capsaicin-induced cough when administered by subcutaneous or inhaled routes. The potencies of baclofen and 3-APPi compared favourably with codeine and dextromethorphan. 4. The GABAB antagonist, CGP 35348 (0.3- 30 mg kg-1, s.c.) inhibited the antitussive effect of baclofen (3.0 mg kg-1, s.c.). However, CGP 35348 (10 mg kg-1, s.c.) had no effect on the antitussive activity of codeine (30 mg kg-1, s.c.). The antitussive effect of baclofen was not influenced by the GABAA antagonist, bicuculline (3 mg kg-1, s.c.) or naloxone (0.3 mg kg-1, s.c.). 5. In the cat, baclofen (0.3-3.0 mg kg-1, i.v.) decreased mechanically-induced cough in a dose-dependent manner. In this model, baclofen (ED50 = 0.63 mg kg-1) was less potent than either codeine or dextromethorphan. The antitussive effect of baclofen in the cat was antagonized by the GABAB antagonists, CGP 35348 (10 mg kg-1, i.v.) and 3-aminopropylphosphonic acid (3 mg kg-1, i.v.).6. We show that baclofen and 3-APPi have antitussive effects in the guinea-pig and cat and these effects are mediated by GABAB receptors.

Animals↗
PubMed1992

Intracardiac phenylbiguanide causes excitation of spinal neurons by activation of cardiac sympathetic afferents.

The responses of spinothalamic, spinoreticular, and unidentified spinal neurons to intracardiac administration of phenylbiguanide, a 5-HT3 receptor agonist, were examined in anesthetized cats and monkeys. Eighteen neurons were excited, 5 were inhibited, and 12 were unresponsive to this stimulus. Results suggest that cardiac sympathetic afferents mediate the excitatory responses produced by phenylbiguanide, because bilateral cervical vagotomy failed to block these responses, and aortic injections of phenylbiguanide had little effect on cell activity.

Adrenergic Fibers↗
PubMed1992

Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons.

1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1992

Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+

Afferent Pathways↗
PubMed1991

Inhibitory effects of phrenic afferent fibers on primate lumbosacral spinothalamic tract neurons.

Studies were conducted to determine if electrical or mechanical stimulation of phrenic afferent fibers (PHR) would inhibit the activity of lumbosacral spinothalamic tract (STT) neurons. Twelve monkeys were anesthetized, paralyzed, and artificially ventilated. Extracellular action potentials were recorded from 78 STT neurons located in L2-S3 spinal segments. Electrical stimulation of PHR reduced the activity of 65%, did not affect 33%, and excited 1% of STT neurons. Mechanical stimulation of the diaphragm reduced the activity of 63%, did not effect 34%, and excited 1% of lumbosacral STT neurons. Distention of the urinary bladder (UBD) inhibited 52%, did not affect 23%, excited 23%, and elicited a biphasic response in 1% of STT neurons. However, there was no correlation between the effect of PHR and UBD or somatic classification of the neurons. We conclude that electrical or mechanical stimulation of PHR can produce a generalized inhibition of lumbosacral STT neurons. This inhibitory effect of PHR is similar to inhibitory effects reported for a variety of other afferent systems.

Action Potentials↗
PubMed1991

Ruthenium red decreases capsaicin and citric acid-induced cough in guinea pigs.

The influence of aerosols of Ruthenium red (RR) on capsaicin- and citric acid-induced cough was investigated in guinea pigs. Aerosols of RR (0.3, 1, 3%) reduced capsaicin-induced cough in dose-dependent manner. Inhalation of RR also reduced cough produced by low, (200 mM) but not high (550 mM), concentrations of citric acid. These data suggest that RR is not a specific capsaicin antagonist and that citric acid and capsaicin share a common mechanism for activation of airway C-fibers that is RR sensitive. Furthermore, high concentrations of citric acid can elicit cough through a RR-insensitive mechanism.

Aerosols↗
PubMed1991

Fictive cough in the cat.

Experiments were performed to determine whether cough could be elicited in paralyzed cats ventilated on a respiratory cycle-triggered pump. Midcollicular decerebrate cats were paralyzed and artificially ventilated on a phrenic-triggered pump. Phrenic and cranial iliohypogastric nerve efferent activities were recorded. Cough was elicited by electrical stimulation of the superior laryngeal nerve (SLN) or probing the intrathoracic trachea. Fictive coughs induced by electrical stimulation of the SLN or mechanical stimulation of the intrathoracic trachea consisted of large-amplitude bursts in phrenic discharge immediately followed by large bursts in cranial iliohypogastric discharge. During fictive cough, phrenic postinspiratory discharge was reduced relative to control cycles. Codeine (0.03-1 mg/kg iv) decreased both SLN- and probe-induced fictive cough. I conclude that fictive cough can be produced in paralyzed cats ventilated on a phrenic-triggered pump. Furthermore, fictive cough can be produced in the absence of afferent feedback associated with active expiration.

Afferent Pathways↗
PubMed1991

Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart.

1. Spinothalamic tract (STT) neurons in the C3-T6 spinal segments were studied for their responses to stimulation of phrenic and cardiopulmonary spinal afferent fibers. A total of 142 STT neurons were studied in 44 anesthetized, paralyzed monkeys (Macaca fascicularis). All neurons were antidromically activated from the ventroposterolateral nucleus and/or medial thalamus. 2. Electrical stimulation of phrenic afferent fibers (PHR) excited 43/58 (74%), inhibited 2/58 (3%), and did not affect 13/58 (13%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of PHR than were neurons with somatic fields confined to the distal limb. Mechanical stimulation of PHR by probing the exposed diaphragm excited 11/22 (50%), inhibited 3/22 (14%), and did not affect 8/22 (36%) cervical STT neurons. 3. The technique of minimum afferent conduction velocity (MACV) was used to obtain information about the identity of the PHR that excited 35 cervical STT neurons. Evidence was obtained for excitation of these neurons by group II and III PHR. The mean +/- SE MACV for all neurons was 14 +/- 2 m/s. 4. Electrical stimulation of cardiopulmonary spinal afferent fibers excited 41/57 (72%), inhibited 8/57 (14%), and did not affect 8/57 (14%) of cervical STT neurons. Neurons with excitatory somatic fields confined to the proximal limb or encompassing the whole limb were excited to a significantly greater extent by electrical stimulation of cardiopulmonary spinal afferents than were neurons with somatic fields confined to the distal limb. 5. Excitatory convergence of PHR and cardiopulmonary spinal afferent input was observed for 36/57 (63%) cervical STT neurons. 6. Electrical stimulation of PHR excited 36/84 (43%), inhibited 25/84 (30%), and did not affect 23/84 (27%) of thoracic STT neurons. All of these neurons received excitatory cardiopulmonary spinal afferent input. 7. Neurons were more likely to be excited by electrical stimulation of PHR if they were located in C3-C6 spinal segments. Furthermore, the net excitatory effect of PHR input decreased in more caudal segments, such that thoracic STT neurons were weakly excited relative to cervical STT neurons. 8. We conclude that cervical STT neurons with excitatory somatic fields that include or are restricted to proximal sites are excited by electrical or mechanical stimulation of PHR. Those effects demonstrate a physiological substrate for pain referred from the diaphragm to the shoulder in patients with pleural effusions or subphrenic abscesses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Effects of intracardiac bradykinin and capsaicin on spinal and spinoreticular neurons.

The responses of thoracic spinal and spinoreticular tract (SRT) neurons to activation of cardiac spinal afferents by injections of bradykinin (BK) and capsaicin (CAP) into the left atrium or pericardial sac were determined in vagotomized cats anesthetized with alpha-chloralose. Activities of spinal and SRT neurons in the T1-T5 spinal cord were recorded extracellularly. All neurons received excitatory somatic and cardiopulmonary sympathetic afferent input. Application of BK and CAP to the heart excited most SRT neurons and many spinal neurons but also inhibited some spinal neurons. The two drugs often affected spinal but not SRT neurons differently. Capsaicin excited high threshold and high threshold inhibitory neurons but not wide-dynamic range spinal neurons. In contrast, BK excited all three categories of spinal and SRT neurons. The differential responses of spinal neurons to intracardiac BK and CAP suggested that these compounds can stimulate functionally different populations of cardiac sympathetic afferents.

Animals↗
PubMed1989

Synaptic effects of intercostal tendon organs on membrane potentials of medullary respiratory neurons.

1. Stimulation of intercostal muscle tendon organs or their afferent fibers reduces medullary inspiratory neuron activity, decreases motor output to inspiratory muscles, and increases the activity of expiratory laryngeal motoneurons. The present study examines the synaptic mechanisms underlying these changes to obtain information about medullary neurons that participate in the afferent limb of this reflex pathway. 2. Membrane potentials of medullary respiratory neurons were recorded in decerebrate paralyzed cats. Postsynaptic potentials (PSPs) elicited in these neurons by intercostal nerve stimulation (INS) were compared before and after intracellular iontophoresis of chloride ions. After chloride injection, the normal hyperpolarization caused by inhibitory (I) PSPs is "reversed" to depolarization. 3. In inspiratory neurons, reversal of IPSPs by chloride injection also reversed hyperpolarization produced by INS when applied during any portion of the respiratory cycle. This observation suggests that increased chloride conductance of the postsynaptic membrane mediated the inhibition. Further, it is very likely that the last-order interneuron in the afferent pathway must be excited by INS and alter inspiratory neuron activity via an inhibitory synapse. The linear relationship between the amplitude of the INS induced PSP and membrane potential of inspiratory neurons provided evidence that neurons in the afferent pathway are not respiratory modulated. 4. The membranes of expiratory vagal motoneurons and post-inspiratory neurons were depolarized by INS during all portions of the respiratory cycle before IPSP reversal. Reversal of IPSPs affected neither this depolarization of expiratory vagal motoneurons during stage I and II expiration nor that of post-inspiratory neurons during stage I expiration. Thus this depolarization probably resulted from synaptic excitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1988

Respiratory pattern changes produced by intercostal muscle/rib vibration.

Large-amplitude vibration of the intercostal muscles/ribs has an inhibitory effect on inspiratory motor output. This effect has been attributed, in part, to the stimulation of intercostal muscle tendon organs. Intercostal muscle/rib vibration can also produce a decrease or increase in respiratory frequency. Studies were conducted 1) to determine whether, in addition to intercostal tendon organs, costovertebral joint mechanoreceptors (CVJR's) contribute to the inspiratory inhibitory effect of intercostal muscle/rib vibration (IMV) and 2) to explain the different respiratory frequency responses to IMV previously reported. Phrenic (C5) activity was monitored in paralyzed thoracotomized, artificially ventilated cats. Vibration (125 Hz) at amplitudes greater than 1,200 micron of one T6 intercostal space in decerebrated vagotomized rats reduced phrenic activity. This response was still present but weaker in some animals after denervation of the T6 intercostal muscles. Subsequent denervation of the T6 CVJR's by dorsal root sections eliminated this effect. Respiratory frequency decreased during simultaneous vibration (greater than 1,200 micron) of the T5 and T7 intercostal spaces in vagotomized cats. Respiratory frequency increased during IMV of two intercostal spaces (greater than 1,300 micron) in vagal intact cats. The use of different anesthetics (pentobarbital, allobarbital) did not alter these results. We conclude that CVJR's may contribute to the inhibitory effect of IMV on medullary inspiratory activity. The presence or absence of pulmonary vagal afferents can account for the different respiratory frequency responses to IMV, and different anesthetics did not influence these results.

Animals↗
PubMed1988

Medullary neurons mediating the inhibition of inspiration by intercostal muscle tendon organs?

Studies were conducted to test the hypothesis that nonrespiratory-modulated units are last-order interneurons mediating the effects of intercostal muscle tendon organs on medullary inspiratory neuron activity. Vagotomized, anesthetized, or decerebrate cats were used. Results show the following. 1) Afferents from different receptor types (i.e., intercostal tendon organs and chest wall cutaneous receptors) that inhibit medullary inspiratory neuron activities evoke the same units. 2) Gastrocnemius muscle group I afferent fibers evoke some of the same units as intercostal afferents but do not alter respiratory activity. 3) The "pneumotaxic center" and laryngeal nerve afferents, which inhibit medullary inspiratory activity, evoke different medullary units than intercostal afferents. 4) Evoked units are not active in spontaneously breathing cats. Additional results suggest that a few respiratory neurons near the retrofacial nucleus may be involved in the mediation of the inspiratory inhibitory effects of intercostal tendon organs. These results do not establish the mechanism by which intercostal muscle tendon organs reduces medullary inspiratory activity.

Afferent Pathways↗
PubMed1987

Medullary inspiratory activity: influence of intercostal tendon organs and muscle spindle endings.

Studies were conducted to determine the effects of intercostal muscle spindle endings (MSEs) and tendon organs (TOs) on medullary inspiratory activity in decerebrate and allobarbital-anesthetized cats. Impeded muscle contractions, elicited by electrical stimulation of the peripheral cut end of the T6 ventral root, were used to stimulate external and internal intercostal TOs without MSEs. Impeded contractions of either the external or internal intercostal muscles reduced phrenic and medullary inspiratory neuronal activities. Vibration was used to selectively stimulate external or internal intercostal MSEs (90 and 40 micron amplitude, respectively). Selective stimulation of either external or internal intercostal MSEs did not change phrenic or medullary inspiratory neuronal activities. It is concluded that both external and internal intercostal TOs have a generalized inhibitory effect on medullary inspiratory activity and intercostal MSEs have no effect on medullary inspiratory activity.

Animals↗
PubMed1987

Medullary expiratory activity: influence of intercostal tendon organs and muscle spindle endings.

Studies were conducted to determine the effects of intercostal muscle spindle endings (MSEs) and tendon organs (TOs) on medullary expiratory activity in decerebrate cats. Impeded intercostal muscle contractions, elicited by electrical stimulation of the peripheral cut end of the T6 ventral root, were used to stimulate intercostal TOs without MSEs. Impeded contractions of the intercostal muscles augmented expiratory laryngeal motoneuron activity, and either had no effect on or reduced the activity of bulbospinal expiratory neurons. Vibration was used to stimulate intercostal MSEs. Intercostal MSEs had no effect on medullary expiratory neuron activity. It is concluded that both external and internal intercostal TOs have an excitatory effect on expiratory laryngeal motoneuron activity and an inhibitory effect on a subpopulation of expiratory neurons driving intercostal and/or abdominal muscles, and intercostal MSEs have no direct influence on medullary expiratory activity.

Animals↗
PubMed1985

Non-vagal reflex effects on medullary inspiratory neurons during inspiratory loading.

Studies were conducted to compare the first-breath responses of medullary Dorsal and Ventral Respiratory Group inspiratory (I) neurons to the mechanical loading (tracheal occlusion, TO) of inspiration in unanesthetized (decerebrate) and anesthetized (Dial) vagotomized cats, and to determine the sources of the sensory activity causing the changes in I-neuron activity. In decerebrate cats, TO resulted in a prolongation of the firing duration in 49% of the I-neurons. There was a delayed onset of firing in 7% of the I-neurons. The responses of I-neurons to TO in anesthetized cats were similar to the responses in decerebrate cats. Changes in I-neuron activity with TO were still present in cats with their cervical (C3-7) or thoracic (T1-9) dorsal roots cut, and absent when both cervical and thoracic dorsal roots were cut. The most probable sources of the cervical and thoracic afferent information altering medullary I-neuron activity during loading are the diaphragm and inspiratory intercostal muscles.

Anesthesia↗