Biomedical subjects

J L Henry

Publications and source records attributed to J L Henry.

At least 91 records · Page 5Linked to original sources

PubMed1991

Responses of functionally identified neurones in the dorsal horn of the cat spinal cord to substance P, neurokinin A and physalaemin.

The mammalian tachykinins, substance P and neurokinin A, and the non-mammalian tachykinin, physalaemin, were tested on functionally identified dorsal horn neurones in vivo. The experiments were done on cats which were anaesthetized with sodium pentobarbital or were anaemically decerebrated. Extracellular single-unit recordings were made in the lumbar spinal cord and the tachykinins were applied by iontophoresis. Each neurone was classified functionally as wide dynamic range, non-nociceptive, nociceptive specific or proprioceptive. The response to tachykinin application was determined for each neurone. Application of each of the tachykinins evoked a characteristic excitatory response which was delayed in onset, slow in developing and prolonged: physalaemin excited 99/131 neurones tested, neurokinin A excited 45/63 neurones and substance P excited 32/49 neurones. With two neurones physalaemin evoked a depression of the rate of firing, which may have been caused indirectly by excitation of a neighbouring neurone. Such depression was not elicited by either substance P or by neurokinin A. Physalaemin had a preferential excitatory effect on nociceptive neurones evoking excitation of 76/94 nociceptive neurones compared with 12/23 non-nociceptive neurones (chi 2 = 7.9, 1 d.f., P = 0.005). Substance P also caused a preferential excitation, with 30/40 nociceptive neurones being excited while all of the non-nociceptive neurones (n = 7) were unaffected (chi 2 = 11.5, 1 d.f., P = 0.0007). In contrast, neurokinin A failed to have a preferential effect; 32/46 nociceptive and 9/10 non-nociceptive neurones were excited (chi 2 = 1.0, 1 d.f., P = 0.40). Comparing the proportions of nociceptive neurones excited by the different tachykinins indicated that this type of neurone was not differently sensitive to any of the three peptides (chi 2 = 3.2, 2 d.f., P = 0.20). On the other hand, non-nociceptive neurones were preferentially excited by neurokinin A and physalaemin compared with substance P (chi 2 = 13.4, 2 d.f., P = 0.001). With regard to the endogenous tachykinins the results of this study may be interpreted in the following ways. The differential excitatory effect of substance P on nociceptive neurones supports the proposed role for this peptide in the transmission specifically of nociceptive inputs at the first afferent synapse. On the other hand, as neurokinin A excited non-nociceptive as well as nociceptive neurones, there may be a functional role for neurokinin A distinct from that of substance P.

Animals↗

PubMed1990

Spinal mediation of the increases in arterial pressure and heart rate in response to intrathecal administration of bicuculline.

The present experiments were designed to determine the mechanisms by which the intrathecal administration of the GABAA antagonist, bicuculline (2.2 and 8.8 nmol), at the second thoracic spinal segment (T2) affects cardiovascular function in the anaesthetized rat. Bicuculline produced a dose-related, transient increase in arterial pressure and heart rate which peaked at 5-7 min and persisted for 30 min or more, depending on dose. There was a mutually reversible interaction between bicuculline and intrathecal administration of the GABAA agonist, muscimol (8.8 nmol), which alone decreased arterial pressure and heart rate. Bicuculline was given intrathecally at the third lumbar spinal level (8.8 nmol) and intravenously (8.8 nmol), but in these cases it failed to affect these cardiovascular parameters. Pretreatment with intrathecal infusion of 15 microliters of 1% lidocaine or with intravenous injection of hexemathonium (10 mg/kg) prevented the responses to intrathecal administration of 8.8 nmol of bicuculline at T2. These results demonstrate that the effects of bicuculline on arterial pressure and heart rate are due to an action in the spinal cord on GABAA receptors, and the data may be interpreted as indicating that there is a tonic GABAergic inhibition of sympathetic outflow at the spinal level.

Animals↗

PubMed1990

Intrathecal administration of delta receptor agonists in the urethane anesthetized rat provokes an increase in arterial pressure via a non-opioid mechanism.

Intrathecal administration of the delta receptor specific agonists Leu5-enkephalin (Leu-Enk; 300 nmol), Met5-enkephalin (Met-Enk; 300 nmol) and [D-Pen2,D-Pen5]enkephalin (DPDPE; 100 nmol) to the T2 or the T9 segment of the rat spinal cord provoked a transient (less than 5 min) increase (15-20 mm Hg) in arterial pressure. DPDPE, but not Leu-Enk or Met-Enk, also significantly increased heart rate by 30-35 bpm. Intravenous administration of 300 nmol of Leu-Enk mimicked the effects observed following intrathecal administration. The hypertensive effect of intrathecal and intravenous Leu-Enk administration was blocked by prior systemic administration (10 mg/kg) of the nicotinic ganglion blocker hexamethonium, suggesting that the effect was mediated via sympathetic activation. The increase in arterial pressure observed following intrathecal Leu-Enk administration was not blocked by either intrathecal (305 nmol) or intravenous (10 mg/kg) administration of the opiate receptor blocker naloxone, although naloxone did block the hypertension provoked by intravenous Leu-Enk administration. Moreover, intrathecal administration of Des-Tyr1-Leu-Enk (300 nmol), an enkephalin fragment devoid of opiate receptor activity, also increased arterial pressure. These results suggest that the hypertension elicited by intrathecal delta agonist administration was not mediated via an opioid mechanism.

Anesthesia↗

PubMed1990

Physiological characteristics of responses of wide dynamic range spinal neurones to cutaneously applied vibration in the cat.

Extracellular single-unit recordings were made from wide dynamic range neurones in the lumbar dorsal horn of anaesthetized or decerebrated cats. Vibration applied to the skin at a frequency of 80 Hz could evoke 3 distinct types of response--excitation, depression or a biphasic response consisting of excitation followed by depression. By applying vibration at different sites, a given neurone was found to show more than one type of response. Parametric studies of the depressant and biphasic responses were made because previous studies indicated that adenosine mediates the depression in these types of response. Thus, amplitude- and frequency-response relationships were determined at individual stimulation sites: amplitude was varied from 0.001 to 1.0 mm (frequency, 80 Hz) and the frequencies studied were 10, 20, 40, 80, 120 and 240 Hz (amplitude, 0.15 mm). Vibration at amplitudes greater than 0.15 mm caused a decrease in the rate of discharge during the period of stimulation, the magnitude of this decrease varying directly with amplitude; at amplitudes of 0.15 mm and less vibration had no statistically significant effect. With regard to the frequency-response relationship, a decrease in discharge rate occurred at frequencies of 120 and 240 Hz, with the more pronounced effect at 240 Hz; excitation occurred at 40 Hz and there was no statistically significant effect at other frequencies. Amplitude- and frequency-response relationships for the depressant and the biphasic responses were analyzed separately. In the case of depressant responses, the magnitude was monotonically related to the amplitude of stimulation and depression occurred only at frequencies of 80 Hz or greater, with higher frequencies being more effective. The biphasic responses appeared to consist of 2 subtypes termed biphasic-1 and biphasic-2 responses. For biphasic-1 responses, the amplitude- and frequency-response curves were similar to those of depressant responses. Biphasic-2 responses differed in that the response was biphasic when the stimulation frequency was 80 Hz or greater and the amplitude was 0.3 mm or more, yet, at lower frequencies and/or amplitudes vibration evoked excitation. The similarities in the amplitude- and frequency-response relationships of depressant and biphasic-1 responses raise the possibility that these responses might be mediated by a single class of primary afferent. Both depressant and biphasic responses were evoked when stimulation parameters (2 microns, 240 Hz) were used which selectively activate Pacinian corpuscle afferents. Depression with 240-Hz stimulation was attenuated by administration of caffeine (60 mg/kg i.v.) suggesting that the depressant and biphasic-1 responses may be mediated by afferents from Pacinian corpuscles.

Action Potentials↗

PubMed1990

Differential responses of nociceptive vs. non-nociceptive spinal dorsal horn neurones to cutaneously applied vibration in the cat.

Extracellular single-unit recordings were made from dorsal horn neurones in the lumbar spinal cord of cats which were anaesthetized or were anaemically decerebrated. Each neurone was classified functionally as wide dynamic range (WDR), non-nociceptive, nociceptive specific or proprioceptive. Vibration was then applied to the hind limb using a feedback-controlled mechanical stimulator. WDR neurones had 3 distinct types of response to vibration (80 Hz: 0.3-1.0 mm): excitation, depression and a biphasic response consisting of excitation followed by depression. The type of response depended upon the location of the stimulator probe. With the stimulator probe placed inside that part of the receptive field from which low intensity, non-vibrational cutaneous stimuli elicited excitation, 35 neurones were excited by the vibratory stimulation, none was depressed and 4 showed the biphasic response. On the other hand, when the probe was positioned outside the receptive field for low intensity stimuli, 7 WDR neurones were excited, 164 showed depression or the biphasic response and 7 were unaffected. On-going activity and activity evoked by iontophoretic application of glutamate were decreased during the depressant response and during the depressant phase of the biphasic response. In terms of non-nociceptive neurones, all (n = 30) were excited by vibration; depressant or biphasic responses were not observed. Excitation was elicited by placing the probe either inside or outside the receptive field for non-vibrational stimuli. All nociceptive specific neurones (n = 3) were depressed by vibration regardless of the position of the stimulus. All proprioceptive neurones (n = 12) were excited by vibration. The predominantly depressant effect of vibration on nociceptive neurones vs. the predominantly excitatory effect on non-nociceptive neurones prompts us to suggest that the increase in pain threshold and the clinical analgesia elicited by vibration may be mediated at the spinal level by a decrease in the rate of firing of nociceptive neurones and/or by excitation of non-nociceptive neurones.

Analgesia↗

PubMed1990

Intrathecal administration of calcitonin gene-related peptide (CGRP) increases heart rate and decreases arterial pressure in the urethane anesthetized rat.

Intrathecal administration of CGRP (2.15-8.60 nmol) to the ninth thoracic vertebral segment of the spinal cord in the urethane anesthetized rat provoked an increase in heart rate (peak effect of 72 bpm) and a decrease in arterial pressure (maximum fall of 15 mmHg). Administration of CGRP to the T2 level (n = 10) or intravenously (n = 6) produced qualitatively and quantitatively similar effects to those observed following administration to the T9 level. The drop in pressure resulting from intrathecal administration was unaffected by prior intrathecal administration of lidocaine (250 micrograms), systemic administration of hexamethonium (5 mg/rat), bilateral vagotomy, or combined bilateral vagotomy/hexamethonium treatment. The failure of these manipulations to alter the hypotension induced by intrathecal CGRP injection suggests that this effect was caused by leakage into the periphery. The cardioacceleration elicited by intrathecal CGRP was attenuated by intrathecal lidocaine administration and by combined bilateral vagotomy/hexamethonium treatment, but not by either treatment alone. These results suggest that CGRP's tachycardic effect is mediated by a direct spinal action involving both sympathetic and parasympathetic mechanisms.

Animals↗

PubMed1990

Adrenal versus nonadrenal sympathetic preganglionic neurones in the lower thoracic intermediolateral nucleus of the cat: effects of serotonin, substance P, and thyrotropin-releasing hormone.

Adrenal and nonadrenal sympathetic preganglionic neurones (SPNs) in the intermediolateral nucleus of spinal segments T8-T10 in the cat were compared according to their responses to iontophoretic application of serotonin, substance P, and thyrotropin-releasing hormone (TRH). Responses of both types of SPN to iontophoretic application of serotonin were characterized by an increase in the rate of discharge that was slow in onset (mean +/- SD = 36 +/- 21 s) and prolonged in afterdischarge (115 +/- 70 s) following termination of application. Depression was never observed and responses were similar whether using serotonin at a pH of 3.3 or 4.5, suggesting that the absence of a depressant effect cannot be accounted for by pH, as has been reported with cortical neurones. Iontophoretic application of methysergide resulted in a decrease in the rate of discharge of both types of SPN and blocked the excitatory responses to serotonin. Adrenal and nonadrenal SPNs were excited by iontophoretic application of substance P. Responses of both types of SPN were similar and were characterized by a gradual increase in the rate of discharge that was slow in onset (42 +/- 27 s) and prolonged in afterdischarge (96 +/- 42 s). Finally, adrenal and nonadrenal SPNs were also weakly excited by iontophoretic application of TRH. These responses were slow in onset (48 +/- 27 s) and prolonged in afterdischarge (78 +/- 35 s). These data indicate that serotonin, substance P, and TRH exert excitatory effects on functionally dissimilar sympathetic preganglionic neurones and support the possibility that they may be chemical mediators of synaptic transmission in the intermediolateral nucleus. In addition, these data may be interpreted to support the notion that serotonin, substance P, and TRH are involved in global activation of the sympathetic nervous system.

Adrenal Glands↗

PubMed1990

Adrenal versus nonadrenal sympathetic preganglionic neurones in the lower thoracic intermediolateral nucleus of the cat: physiological properties.

Adrenal and nonadrenal sympathetic preganglionic neurones (SPNs) in the intermediolateral nucleus of spinal segments T8-T10 in the cat were compared according to a number of physiological properties. An SPN was classified as "adrenal" (n = 37) if it could be antidromically activated by electrical stimulation of the adrenal medulla. An SPN that could not be activated from the adrenal medulla yet could be antidromically activated by electrical stimulation of the greater splanchnic nerve was classified as "nonadrenal" (n = 123). Approximately 50% of adrenal SPNs (17 out of 37) were activated antidromically by stimulation of both the greater splanchnic nerve and adrenal medulla, suggesting that these neurones projected to the adrenal medulla via the greater splanchnic nerve, with the other adrenal SPNs taking a different route. The mean conduction velocities of adrenal (6.7 +/- 1.8 (SD) m/s) and nonadrenal (6.7 +/- 1.5 m/s) sympathetic preganglionic axons were similar. Over 80% of adrenal (31 out of 37) and nonadrenal (104 out of 116) SPNs were spontaneously active. The two types of neurone were indistinguishable in terms of the rates and patterns of discharge. Adrenal SPNs discharged with a mean rate of 1.4 +/- 1.1 spikes/s, and nonadrenal SPNs discharged with a mean rate of 1.8 +/- 1.4 spikes/s. With both types of SPN, the pattern of spontaneous activity was either irregular or phasic. With the latter pattern, periodic bursts of discharge were at the same frequency as oscillations in arterial pressure, frequency of ventilation, or phrenic nerve discharge. These data suggest that adrenal and nonadrenal sympathetic preganglionic neurones in the intermediolateral nucleus in caudal thoracic segments share a number of common physiological properties.

Adrenal Glands↗

PubMed1989

Cardiovascular responses to intrathecal administration of strychnine in the rat.

Experiments were done to determine the influence of spinal glycinergic mechanisms in regulating sympathetic output to the heart and vessels in the anaesthetized male Sprague-Dawley rat. Intrathecal administration of 65 (n = 6) and 130 (n = 8) nmol of strychnine, but not of a lower dose (32.5 nmol, n = 8), to the second thoracic segment increased heart rate within one minute (P less than 0.01). Similar administration of artificial cerebrospinal fluid (n = 16) had no effect. The increase in heart rate in response to strychnine peaked at 5-7 min (+35.1 +/- 5.8 bpm with 130 nmol), and slowly returned toward baseline values over the next 25 min. Arterial pressure was unaffected by this treatment. These effects were not mimicked by administration of strychnine (n = 6) at the third lumbar spinal level or by intravenous infusion of strychnine (n = 4) and were abolished by systemic injection of hexamethonium (n = 6). The results suggest that there is a tonic glycine-mediated inhibition of sympathetic output at the spinal level.

Adrenergic Fibers↗

PubMed1989

Bombesin, neuromedin B and neuromedin C selectively depress superficial dorsal horn neurones in the cat spinal cord.

The effects of bombesin and related peptides on functionally identified single dorsal horn neurones were studied using iontophoresis and extracellular recording in the anaesthetized and spinalized cat. Bombesin selectively depressed superficial dorsal horn neurones (in laminae I-III). The depression was of spontaneous activity as well as of synaptically elicited responses to natural stimulation of the cutaneous receptive field. Bombesin preferentially depressed neurones that responded to noxious stimulation of the cutaneous receptive field. Naloxone, bicuculline and caffeine failed to block the depression by bombesin, suggesting that the effect of the peptide may be direct and not through the indirect activation of an inhibitory system mediated by opioids, by gamma-aminobutyric acid (GABA) or by purines, respectively. Iontophoretic application of neuromedin B (n = 3) and neuromedin C (GRP-10) (n = 7) induced a similar depression to that observed with bombesin. These results provide physiological evidence that a bombesin-like peptide may play a role in the mediation or the modulation of sensory transmission in the superficial dorsal horn of the spinal cord.

Action Potentials↗

PubMed1989

Intrathecal administration of CGRP in the rat attenuates a facilitation of the tail flick reflex induced by either substance P or noxious cutaneous stimulation.

Intrathecal (i.t.) administration of substance P in the awake rat decreases reaction time (RT) in the tail flick test. In the anaesthetized rat, noxious thermal stimulation of the tail (by immersion of tip in water at 55 degrees C) also decreases RT; this effect is blocked by a substance P antagonist. The present study examines the effects of calcitonin gene-related peptide (CGRP) on the decrease in RT produced in these two paradigms. Pretreatment with CGRP (3.25 nmol, i.t.) attenuated and abolished the decreases in RT produced by substance P (3.25 nmol, i.t.) and by noxious cutaneous stimulation, respectively. These results indicate an interaction of CGRP and substance P in the regulation of the tail flick reflex.

Analysis of Variance↗

PubMed1989

Vasopressin and oxytocin express excitatory effects on respiratory and respiration-related neurones in the nuclei of the tractus solitarius in the cat.

The effects of the iontophoretic application of vasopressin and oxytocin were examined on the activity of single neurones recorded in the region of the nuclei of the tractus solitarius (NTS) of the cat that were functionally classified as respiratory neurones or presumed reflex interneurones. The excitatory effects observed in half to two-thirds of these neurones tested (n = 37) suggest a role of these peptides in respiratory control and further support recent evidence that their involvement in autonomic control may include an action in NTS.

Action Potentials↗

PubMed1989

Neural mechanisms of swallowing: neurophysiological and neurochemical studies on brain stem neurons in the solitary tract region.

Neurophysiological studies of the nuclei of the tractus solitarius (NTS) and adjacent regions have provided a partial understanding of the integrative brainstem network underlying swallowing and related functions such as respiration. The NTS is also richly endowed with an abundance of neuropeptides and other neuroactive substances, but only limited information is available on their influences on neurons involved specifically in swallowing. Since dysfunction of these neurophysiological and neurochemical regulatory mechanisms in the NTS region may be important in pathophysiological conditions such as dysphagia, increased awareness of and focus on these mechanisms are warranted. This paper outlines recent neurophysiological and neurochemical data that provide information on the afferent inputs and neurophysiological properties of neurons in NTS and adjacent caudal brainstem regions implicated in swallowing, respiration, and respiratory-related reflexes.

Angiotensin II↗

PubMed1989

Angiotensin II stimulates sympathetic output by a direct spinal action.

When administered intrathecally in a dose of 10 mu to the ninth thoracic segment of the spinal cord in the anesthetized rat, angiotensin II produced a transient increase in systolic and diastolic arterial pressures lasting 1-4 min. Heart rate was also increased, but in this case for more than 30 min. Similar administration of 5 micrograms or of CSF had no effect on either arterial pressure or heart rate. Neither the arterial pressure nor the heart rate response to 10 micrograms of angiotensin II was observed in rats given hexamethonium (10 mg/kg, i.v.), suggesting that the effects were mediated by spinal activation of sympathetic output. When the rats were pretreated with 10 micrograms of [Sar1, IIe8]-angiotensin II three min prior to angiotensin II, there was a block of the increase in arterial pressure but not of the increase in heart rate. When the antagonist was given 15 min prior to angiotensin II, the full pressor response appeared, suggesting that the antagonist was effective for less than 15 min; in addition, after the antagonist alone, while arterial pressure remained unaltered, there was a gradual increase in heart rate suggesting that the analogue had agonistic effects on mechanisms regulating heart rate. These results suggest that angiotensin II activates sympathetic mechanisms by a spinal action and that arterial pressure and heart rate are regulated differentially, arterial pressure via a mechanism which is antagonized by [Sar1, IIe8]-angiotensin II, and heart rate via a mechanism in which the analog can act as an agonist.

Angiotensin II↗

PubMed1989

Thyrotropin-releasing hormone given intrathecally to the rat increases arterial pressure and heart rate.

In view of evidence implicating thyrotropin-releasing hormone (TRH) as a chemical mediator of synaptic transmission onto spinal sympathetic neurons, this peptide was administered intrathecally, in a dose of 6.5 nmol, at the T9 and T2 spinal levels in the anesthetized rat. At the lower thoracic level TRH increased arterial pressure and heart rate; these effects peaked at 4-7 minutes and decayed over the next 15-20 minutes. At the upper thoracic level the pressor and cardioacceleratory responses were roughly similar in time course but were smaller in magnitude. Hexamethonium (10 mg/kg i.v.) was tested on the responses from the lower thoracic level; both pressor and cardioacceleratory responses persisted after hexamethonium pretreatment. In addition, intravenous administration of 6.5 nmol of TRH failed to alter arterial pressure or heart rate, suggesting that the effects produced by the intrathecal administration of TRH were due to an action of the peptide in the spinal cord. The results also indicate that the pressor effect and the increase in heart rate may be mediated in the sympathetic ganglia at least partly via nonnicotinic transmission. Our results provide physiological support for the possibility that TRH is a chemical mediator of synaptic transmission onto sympathetic preganglionic neurons. This study indicates that the functional sympathetic pathways utilizing TRH as a chemical mediator include those regulating arterial pressure and heart rate.

Animals↗

PubMed1989

Concepts of pain sensation and its modulation.

A review of the recent literature is presented on the basic physiological mechanisms by which pain (nociceptive) information is transferred in the peripheral and central nervous systems, as well as how this transmission is modified or modulated by endogenous mechanisms known to produce analgesia. The specific topics covered include the first sensory nerve fibers which conduct pain information into the spinal cord, the physiological properties and anatomical organization of the spinal cord mechanisms for transmission and modulation, the chemicals involved in synaptic transfer of information from the first to the second neurone in the sensory pathway and the major ascending nociceptive and descending antinociceptive pathways.

Afferent Pathways↗

PubMed1989

Transforming growth factor alpha and its receptor in neural retina.

Transforming growth factor alpha (TGF-alpha) stimulates mitosis of many ectodermal cells but has not previously been studied for its role in neural tissues such as retina. We examined bovine retina for the presence of TGF-alpha mRNA, TGF-alpha protein and for the presence and location of the TGF-alpha/EGF receptor. Biochemical studies demonstrated a high level (770 fmol/mg protein) of specific, high affinity (Kd = 2 nM) TGF-alpha/EGF receptors in membrane homogenates of neural retina, but undetectable binding to homogenates of retinal pigment epithelium. Light microscopic autoradiograms of sections of neural retinal tissue incubated with 125I-EGF indicated that specific TGF-alpha/EGF receptors were present on one or more cell types of the retina with the exception of the outer segments of the photoreceptor cells. In addition, retinal cells appear to synthesize TGF-alpha since both mRNA for TGF-alpha and TGF-alpha protein (4.2 ng/mg protein) were detected in retinal extracts using cDNA hybridization and TGF-alpha RIA techniques. The role(s) of TGF-alpha and its receptor in retina is unknown, but it is possible that they interact via an autocrine/paracrine mechanism to influence retinal regeneration, proliferative retinopathies or neural transmission.

Animals↗

PubMed1988

Facilitation of the tail-flick reflex by noxious cutaneous stimulation in the rat: antagonism by a substance P analogue.

Effects of noxious cutaneous stimulation on the tail flick reflex were examined in the anaesthetized rat. Noxious stimulation was applied by immersing the distal 4 cm of the tail in water at 55 degrees C for 1.5 min. The tail flick reflex was tested at 3 min intervals by applying a noxious radiant heat stimulus to a region of the tail 10 cm proximal to the tip. Tail immersion reduced reaction time to tail flick by 30% and 20% at 0.5 and 3.5 min after immersion, respectively. Reaction time returned to control at 6.5 min and tended to increase above baseline values at 9.5 and 12.5 min. Naloxone (10 mg/kg, i.p.) potentiated the effects of tail immersion on reaction time and prevented the increase above baseline. When the surface temperature of the skin used to evoke the tail flick reflex was raised by 10 degrees C using innocuous radiant heat, reaction time was not significantly different from the control, suggesting that an increase in skin temperature per se is insufficient to account for the response to immersion. Intrathecal administration of a substance P antagonist (1 nmol) attenuated the response to tail immersion. These results indicate that noxious cutaneous stimulation may release an agent in the spinal cord which facilitates the tail flick reflex, and that this agent is antagonized by a substance P antagonist.

Animals↗